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Adult Rats (adult + rat)
Kinds of Adult Rats Terms modified by Adult Rats Selected AbstractsMagnetic Resonance Imaging in the Study of the Lithium,Pilocarpine Model of Temporal Lobe Epilepsy in Adult RatsEPILEPSIA, Issue 4 2002Catherine Roch Summary: ,Purpose: In temporal lobe epilepsy, it remains to be clarified whether hippocampal sclerosis is the cause or the consequence of epilepsy. We studied the temporal evolution of the lesions in the lithium,pilocarpine model of epilepsy in the rat with magnetic resonance imaging (MRI) to determine the progressive morphologic changes occurring before the appearance of chronic epilepsy. Methods: MRI was performed on an MR scanner operating at 4.7 T. We followed the evolution of lesions using T2 - and T1 -weighted sequences before and after the injection of gadolinium from 2 h to 9 weeks. Results: At 2 h after status epilepticus (SE), a blood,brain barrier breakdown could be observed only in the thalamus; it had disappeared by 6 h. At 24 h after SE, edema was present in the amygdala and the piriform and entorhinal cortices together with extensive neuronal loss; it disappeared progressively over a 5-day period. During the chronic phase, a cortical signal reappeared in all animals; this signal corresponded to gliosis, which appeared on glial fibrillary acidic protein (GFAP) immunohistochemically stained sections as hypertrophic astrocytes with thickened processes. In the hippocampus, the correlation between histopathology and T2 -weighted signal underscored the progressive constitution of atrophy and sclerosis, starting 2 days after SE. Conclusions: These data show the reactivity of the cortex that characterizes the initial step leading to the development of epilepsy and the late gliosis that could result from the spontaneous seizures. Moreover, it appears that hippocampal sclerosis progressively worsened and could be both the cause and the consequence of epileptic activity. [source] Blunted Pituitary-Adrenocortical Stress Response in Adult Rats Following Neonatal Dexamethasone TreatmentJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2000K. Felszeghy Abstract Glucocorticoids have a prominent impact on the maturation of the stress-related neuroendocrine system and on the postnatal establishment of adaptive behaviour. The present study aimed at investigating the stress responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis in young and adult rats after neonatal treatment with the synthetic glucocorticoid agonist, dexamethasone. Newborn male Wistar rats were injected s.c. with 1 µg/g dexamethasone on postnatal days 1, 3 and 5. Circulating adrenocorticotropic hormone (ACTH) and corticosterone concentrations were measured in the resting state and following a 30-min cold stress at the age of 10 days, as well as after a 30-min restraint stress at the age of 14 weeks. Also in adults, pituitary and adrenocortical hormone responsiveness was evaluated after i.v. administration of 2 µg/kg corticotropin releasing hormone (CRH). In addition, glucocorticoid (GR) and mineralocorticoid receptor (MR) binding capacities were assessed in the pituitaries of adult rats. The results showed that at day 10 basal ACTH concentration was elevated while the cold stress-evoked ACTH response was attenuated in the dexamethasone-treated rats. As adults, treated rats showed a suppressed elevation of both ACTH and corticosterone plasma cncentrations in response to restraint, while basal hormonal concentrations were not altered. There was no difference in the magnitude of the CRH-induced elevation of ACTH and corticosterone concentrations initially; however, the dexamethasone-treated animals showed a prolonged secretion of both hormones. These animals also showed a selective decrease in pituitary GR binding capacity. Neonatal dexamethasone treatment strongly suppressed body weight gain, and adrenal and thymus weights in the early phase of postnatal development. By adulthood, the body and adrenal weights were normalized while thymus weight was greater than in controls. These findings indicate that neonatal dexamethasone treatment permanently alters HPA axis activity by reducing stress responses to cold and restraint probably through supra-pituitary actions, and by decreasing the effectiveness of feedback through a diminished GR binding in the pituitary. [source] Interactions of Stress and CRF in Ethanol-Withdrawal Induced Anxiety in Adolescent and Adult RatsALCOHOLISM, Issue 9 2010Tiffany A. Wills Background:, Repeated stress or administration of corticotropin-releasing factor (CRF) prior to ethanol exposure sensitizes anxiety-like behavior in adult rats. Current experiments determined whether adolescent rats were more sensitive to these challenges in sensitizing ethanol withdrawal-induced anxiety and altering CRF levels in brain during withdrawal. Methods:, Male adult and adolescent Sprague,Dawley rats were restraint stressed (1 hour) twice 1 week apart prior to a single 5-day cycle of ethanol diet (ED; stress/withdrawal paradigm). Other rats received control diet (CD) and three 1-hour restraint stress sessions. Rats were then tested 5, 24, or 48 hours after the final withdrawal for anxiety-like behavior in the social interaction (SI) test. In other experiments, adolescent rats were given two microinjections of CRF icv 1 week apart followed by 5 days of either CD or ED and tested in social interaction 5 hours into withdrawal. Finally, CRF immunoreactivity was measured in the central nucleus of the amygdala (CeA) and paraventricular nucleus (PVN) after rats experienced control diet, repeated ethanol withdrawals, or stress/withdrawal. Results:, Rats of both ages had reduced SI following the stress/withdrawal paradigm, and this effect recovered within 24 hours. Higher CRF doses were required to reduce SI in adolescents than previously reported in adults. CRF immunohistochemical levels were higher in the PVN and CeA of CD-exposed adolescents. In adolescent rats, repeated ethanol withdrawals decreased CRF in the CeA but was not associated with decreased CRF cell number. There was no change in CRF from adult treatments. Conclusions:, In the production of anxiety-like behavior, adolescent rats have equal sensitivity with stress and lower sensitivity with CRF compared to adults. Further, adolescents had higher basal levels of CRF within the PVN and CeA and reduced CRF levels following repeated ethanol withdrawals. This reduced CRF within the CeA could indicate increased release of CRF, and future work will determine how this change relates to behavior. [source] Sensitization, Duration, and Pharmacological Blockade of Anxiety-Like Behavior Following Repeated Ethanol Withdrawal in Adolescent and Adult RatsALCOHOLISM, Issue 3 2009Tiffany A. Wills Background:, Repeated ethanol withdrawal sensitizes anxiety-like behavior in adult rats and causes anxiety-like behavior and decreased seizure thresholds in adolescent rats. Current experiments determined if adolescent rats exhibit sensitized anxiety-like behavior, the duration of this effect, if drug pretreatments blocked these effects, and if these effects differed from those seen in adults. Methods:, Male adolescent rats received three 5-day cycles of 2.5% ethanol diet (ED) separated by two 2-day withdrawal periods, continuous 15 days of 2.5%ED, or a single 5-day cycle of 2.5%ED. Male adult rats received three 5-day cycles of either 2.5% or 3.5%ED. These groups were tested 5 hours into the final withdrawal for social interaction (SI) deficits (an index of anxiety-like behavior). Ethanol intake was monitored throughout and blood concentrations were obtained from separate groups of rats. Additionally, adolescent rats were tested for SI 1, 2, 7, 14, and 18 days and adults 1 and 2 days after the final withdrawal. Some adolescent rats were also pretreated with the CRF1 antagonist CP-154,526, the 5-HT1A agonist buspirone, or the benzodiazepine receptor antagonist flumazenil during the first 2 withdrawals. Results:, SI was reduced in adolescent rats following repeated withdrawals of 2.5%ED while neither a continuous or single cycle ED exposure caused this effect. Adult rats also had reduced SI following repeated withdrawals from both 2.5% and 3.5%ED. This effect was present up to 1 week following the final withdrawal in adolescents but returned to baseline by 1 day in adults. CP-154,526, buspirone, or flumazenil prevented this reduction in SI in adolescent rats. Conclusions:, Adolescent rats exhibit sensitized anxiety-like behavior following repeated withdrawals at ED concentrations similar to those used in adults. However, this effect is longer lasting in adolescent rats. Drugs modulating CRF, 5-HT, or GABA systems during initial withdrawals prevent the development of anxiety-like behavior otherwise manifest during a final withdrawal in adolescent rats. [source] Differential Dietary Ethanol Intake and Blood Ethanol Levels in Adolescent and Adult Rats: Effects on Anxiety-Like Behavior and Seizure ThresholdsALCOHOLISM, Issue 8 2008Tiffany A. Wills Background:, Adult rats exhibit increased anxiety-like behavior after exposure to repeated cycles of chronic ethanol and withdrawal. While adolescent rats have differential responses to both acute and chronic ethanol treatments, the potential differences in the effects of repeated withdrawals in this population have yet to be determined. Methods:, Male adult and adolescent rats received three 5-day cycles of either a 4.5% or 7% ethanol diet (ED) separated by two 2-day withdrawal periods. Five hours into the final withdrawal, rats were tested for social interaction (SI) deficits (an index of anxiety-like behavior) and then assessed for seizure thresholds (audiogenic and bicuculline-induced). Ethanol intake was monitored throughout, and blood ethanol concentrations (BEC) were obtained from a separate group of rats. Results:, Adolescent rats have reduced SI during the final withdrawal from either ED and exhibit a greater reduction in SI compared to adult rats when exposed to a 7%ED. Audiogenic seizures were not increased during withdrawal from either ED in adult rats, but adolescent rats that received 7%ED displayed increased seizures. The bicuculline seizure thresholds were decreased in both ages exposed to a 7%ED, but only adolescent rats showed this decreased threshold after 4.5%ED. Ethanol intakes and BECs were higher in adolescent rats compared to similarly treated adults. However, ethanol intakes and BECs were comparable between 4.5%ED-treated adolescent and 7%ED-treated adult rats. Conclusions:, Behavioral results from the 7%ED-treated groups suggested that adolescent rats may be more vulnerable to repeated withdrawals from ethanol than adults; however, differences in ethanol intake and BECs may be at least in part responsible. When ethanol intakes and BECs were similar between 4.5%ED-treated adolescent and 7%ED-treated adult rats, behavioral effects were not different. Importantly, these data illustrated that adolescent rats can exhibit anxiety and reduced seizure thresholds following this repeated withdrawal paradigm. [source] Time Course of Elevated Ethanol Intake in Adolescent Relative to Adult Rats Under Continuous, Voluntary-Access ConditionsALCOHOLISM, Issue 7 2007Courtney S. Vetter Background: Adolescence is a period of elevated alcohol consumption in humans as well as in animal models. Previous studies in our laboratory have shown that adolescent Sprague,Dawley rats consume approximately 2 times more ethanol on a gram per kilogram basis than adult animals in a 2-bottle choice free-access situation. The purpose of the present study was to examine the time course and pattern of elevated ethanol intake during adolescence and the adolescent-to-adult transition, contrast this intake with ontogenetic patterns of food and water intake, and determine whether adolescent access to ethanol elevates voluntary consumption of ethanol in adulthood. Methods: Adolescent [postnatal day (P)27,28] and adult (P69,70) male Sprague,Dawley rats were singly housed with continuous access to both water and 1 of 3 experimental solutions in ball-bearing,containing sipper tubes: unsweetened ethanol (10% v/v), sweetened ethanol (10% v/v+0.1% w/v saccharin), and saccharin alone (0.1% w/v). Results: Ethanol consumption plateaued at approximately 7.5 g/kg/d during the first 2 weeks of measurement (i.e., P28,39) in early adolescence, before declining sharply at approximately P40 to levels that were only modestly elevated compared with adult-typical consumption patterns that were reached by approximately P70. In contrast, intake of food and total calories showed a more gradual decline into adulthood with no distinguishable plateaus in early adolescence. When adolescent-initiated and adult-initiated animals were tested at the same chronological age in adulthood, animals drank similar amounts regardless of the age at which they were first given voluntary access to ethanol. Conclusions: Taken together, these data suggest that the elevated ethanol intake characteristic of early-to-mid adolescence is not simply a function of adolescent-typical hyperphagia or hyperdipsia, but instead may reflect age-related differences in neural substrates contributing to the rewarding or aversive effects of ethanol, as well as possible modulatory influences of ontogenetic differences in sensitivity to novelty or in ethanol pharmacokinetics. Voluntary home cage consumption of ethanol during adolescence, however, was not found to subsequently elevate ethanol drinking in adulthood. [source] Nicotine Decreases Blood Alcohol Concentrations in Adult Rats: A Phenomenon Potentially Related to Gastric FunctionALCOHOLISM, Issue 8 2006Scott E. Parnell Background: In spite of the fact that drinking and smoking often occur together, little is known about the pharmacokinetic interaction between alcohol and nicotine. Previous research in neonatal rats demonstrated that nicotine reduces blood alcohol concentrations (BACs) if alcohol and nicotine are administered simultaneously. However, it is unclear whether such a phenomenon can be observed in adult subjects, given the fact that there is an ontogenetic difference in alcohol metabolism. Methods: A range of nicotine doses (0, 0.25, 0.5, 1, 2, 4, and 6 mg/kg) were administered individually with an alcohol dose (4 g/kg) via intragastric (IG) intubation to adult female rats, and the resultant BACs were measured at various time points following drug administration. Furthermore, the hypothesis that nicotine's role in reducing BACs is mediated through factors related to gastric function was examined by comparing the resultant BACs after an IG intubation or intraperitoneal (IP) injection of alcohol. Results: The results from this study showed significant nicotine dose,related decreases in BACs with 0.5, 1, 2, 4, and 6 mg/kg doses of nicotine at the various time points assessed. This effect, however, occurred only when alcohol was administered via IG intubation, but not after an IP injection of alcohol. Conclusions: These results suggest that the nicotine-induced decrease in BAC may be related to gastric function. One possible explanation was related to nicotine's action in delaying gastric emptying. The longer the alcohol was retained in the stomach, the more likely that the alcohol would be metabolized by gastric alcohol dehydrogenase before its absorption into the bloodstream by the small intestine (the major site of alcohol absorption). [source] Binge Pattern Ethanol Exposure in Adolescent and Adult Rats: Differential Impact on Subsequent Responsiveness to EthanolALCOHOLISM, Issue 8 2000Aaron M. White Background: Recent evidence indicates that adolescent animals are more sensitive than adults to the disruptive effects of acute ethanol exposure on spatial learning. It is not yet known whether adolescent animals are also more sensitive than adults to the enduring neurobehavioral effects of repeated ethanol exposure. In this study, animals were exposed to ethanol in a binge-pattern during either adolescence or adulthood. At a time when all subjects were adults, spatial working memory was examined in the absence and presence of an acute ethanol challenge. Methods: Rats were exposed to ethanol (5.0 g/kg intraperitoneally) or isovolumetric saline at 48 hr intervals over 20 days. Exposure began on either postnatal day 30 (adolescent group) or 70 (adult group). Twenty days after the final injection, a time at which all animals were adults, the subjects were tested on an elevated plus maze and then were trained to perform a spatial working memory task on an eight-arm radial maze. At the beginning of each session of training on the working memory task, subjects retrieved food rewards on four of the eight arms. After a delay, subjects were placed on the maze and allowed to retrieve food from the remaining four arms. Results: Prior exposure to ethanol did not influence behavior on the plus maze. Performance of the groups did not differ during acquisition of the spatial working memory task with a 5 min delay or during subsequent testing with a 1 hr delay. However, animals treated with ethanol during adolescence exhibited larger working memory impairments during an ethanol challenge (1.5 g/kg intraperitoneally) than subjects in the other three groups. Conclusions: The findings indicate that binge pattern exposure to ethanol during adolescence enhances responsiveness to the memory-impairing effects of ethanol in adulthood. [source] Inhibition of Canonical Wnt Signaling Increases Microvascular Hemorrhaging and Venular Remodeling in Adult RatsMICROCIRCULATION, Issue 5 2010JASON T. GLAW Microcirculation (2010) 17, 348,357. doi: 10.1111/j.1549-8719.2010.00036.x Abstract Objective:, The canonical Wnt signaling pathway, heavily studied in development and cancer, has recently been implicated in microvascular growth with the use of developmental and in vitro models. To date, however, no study exists showing the effects of perturbing the canonical Wnt pathway in a complete microvascular network undergoing physiological remodeling in vivo. Our objective was to investigate the effects of canonical Wnt inhibition on the microvascular remodeling of adult rats. Methods:, Canonical Wnt inhibitor DKK-1, Wnt inhibitor sFRP-1, BSA or saline was superfused onto the exteriorized mesenteric windows of 300 g adult female Sprague-Dawley rats for 20 minutes. Three days following surgery, mesenteric windows were imaged intravitally and harvested for immunofluorescence staining with smooth muscle alpha-actin and BRDU. Results:, We observed prominent differences in the response of the mesenteric microvasculature amongst the various treatment groups. Significant increases in hemorrhage area, vascular density, and draining vessel diameter were observed in windows treated with Wnt inhibitors as compared to control-treated windows. Additionally, confocal imaging analysis showed significant increases in proliferating cells as well as evidence of proliferating smooth muscle cells along venules. Conclusions:, Together, our results suggest that canonical Wnt inhibition plays an important role in microvascular remodeling, specifically venular remodeling. [source] Decreased Arteriolar Sensitivity to Shear Stress in Adult Rats is Reversed by Chronic Exercise ActivityMICROCIRCULATION, Issue 2 2002Dong Sun M.D., Ph.D. Objective: We tested the hypothesis that the decline in endothelium-dependent arteriolar dilation in adult rats is reversed by chronic exercise activity. Methods: Rats were divided into young (8,10 weeks)-sedentary (SEDY), adult (29,32 weeks)-sedentary (SEDA), and adult-exercised (EXA, treadmill exercise for 18,20 weeks) groups. Responses of isolated arterioles (,50 µm at 80 mm Hg) of gracilis muscle were assessed to increases in perfusate flow and vasoactive agents. Results: With no differences in basal tone, maximal flow-induced dilations were not different between arterioles of SEDY and SEDA rats (71 ± 2 and 72 ± 2% of passive diameter, respectively), yet the sensitivity of arterioles to shear stress (WSS50) was significantly less in SEDA than in SEDY rats (35 ± 4 vs. 23 ± 3 dyne/cm2, respectively). In vessels of EXA rats, maximal flow-induced dilation was significantly augmented (88 ± 2% of passive diameter) and WSS50 (15 ± 1 dyn/cm2) was significantly reduced. Dilation to acetylcholine was enhanced in arterioles of EXA, whereas dilation to sodium nitroprusside was not different in vessels of the three groups. Conclusion: Chronic exercise activity reverses age related reduction in sensitivity of arterioles to increases in wall shear stress. [source] Oestradiol Induced Inhibition of Neuroendocrine Marker Expression in Leydig Cells of Adult RatsREPRODUCTION IN DOMESTIC ANIMALS, Issue 3 2006HH Ortega Contents The objectives of this work were to determine the changes in the expression of neuroendocrine markers in Leydig cell by oestradiol treatment, and to determine whether testosterone is able to recover partially the effects of hormonal suppression induced by oestradiol. Adult male rats were injected daily with either 50 ,g of oestradiol or oestradiol plus testosterone propionate (25 mg every 3 days) for 15 days. The animals were sacrificed and testicles were dissected and processed by routine histological protocols. FSH and LH serum levels were determined by radioimmunoassay. The visualization of antigens was achieved by the streptavidin-peroxidase immunohistochemical method. Antibodies against chromogranin A (CrA), S-100 protein (S-100), P substance (PS), synaptofisin (SYN), neurofilament protein (NF), gliofibrillary acidic protein (GFAP) and neuron specific enolase (NSE) were used. The mean LH and FSH serum concentrations were consistently suppressed with hormonal treatments. Intermediate filaments (NF and GFAP) showed no difference in their expression. The expression of S-100, NSE and SYN was significantly lower in both hormone-treated groups. In oestradiol-treated rats, the immunoreactivity of CrA and SP decreased significantly but was restored after testosterone supplementation. Although the nature and functions of many of these substances in Leydig cells remain unknown, these results are consistent with the hypothesis that the expression of some neuroendocrine markers is hormonally controlled. [source] Repeated exposures to gustatory stimuli produce habituation or positive contrast effects in perinatal ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2004G. Andrew Mickley Abstract Adult rats exhibit a decrease in consummatory responses following repeated presentations of a taste (habituation) and an increase in consummatory responses if they experience an upward shift in the magnitude or intensity of a gustatory stimulus (e.g., sucrose or saccharin). These responses do not represent a direct sensorimotor reaction to a gustatory cue, but rather reflect a change in responding based on the memory of a previous taste. Here, we sought to determine if fetal rats could (like adults) adjust their orofacial motor responses based on a memory of recent gustatory experience. Embryonic Day 18 (E18) or Day 19 (E19) rat fetuses received oral lavage with either 0.15 or 0.30% saccharin (SAC). Subsequently, observations of orofacial movements (mouthing and licking) following oral lavage with 0.30% SAC were made 50 min later, 24 hr later, or on postnatal Day 3 (P3). Thus, some animals were in a "shifted" condition in which they first experienced a relatively low concentration of SAC and then a higher one while control rats ("nonshifted") received 0.30% SAC during both taste exposures. Fetuses exhibited evidence of both habituation (with repeated presentation of the 0.30% SAC) and positive contrast effects (PCEs) (following an upward shift in SAC concentration) when retested 50 min after their first exposure to SAC on E19. However, these animals did not exhibit PCEs 24 hr later or 5 days later (on P3). Contrast effects were not observed when the initial SAC exposure was on E18, and habituation responses were variable depending on the time interval between the taste presentations to these animals. Rats with a 5- to 6-day latency between the two taste presentations showed neither PCEs nor habituation. Our data indicate that PCEs and habituation effects emerge at different ages, and their demonstration is dependent upon the latency between the taste presentations. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 176,188, 2004. [source] 5,7-dihydroxytryptamine lesions enhance and serotonergic grafts normalize the evoked overflow of acetylcholine in rat hippocampal slicesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2002Anja Birthelmer Abstract Adult rats were subjected to intracerebroventricular injections of 5,7-dihydroxytryptamine (5,7-DHT; 150 µg) and, 15 days later, to intrahippocampal grafts of fetal raphe cell suspensions. About 11 months later, we assessed baseline and electrically evoked release of tritium ([3H]) in hippocampal slices, preloaded with tritiated ([3H])choline or [3H]serotonin (5-HT), in the presence or absence of the 5-HT1B receptor agonist CP-93,129 and the 5-HT receptor antagonist methiothepine. HPLC determinations of monoamine concentrations were also performed. The lesions reduced the concentration of 5-HT (,90%) and the accumulation (,80%) as well as the evoked release (,90%) of [3H]5-HT. They also decreased the inhibitory effects of CP-93,129 on the evoked release of [3H]5-HT. Most interestingly, they facilitated the evoked release of [3H]acetylcholine (+20%). In slices from rats subjected to lesions and grafts, the responsiveness of the serotonergic autoreceptors (presumably located on the terminals of the grafted neurons) and the release of acetylcholine were close to normal. These results confirm that grafts rich in serotonergic neurons may partially compensate for the dramatic effects of 5,7-DHT lesions on serotonergic hippocampal functions. The lesion-induced reduction of the 5-HT1B autoreceptor-mediated inhibition of evoked 5-HT release may be an adaptation enhancing serotonergic transmission in the (few) remaining terminals. The facilitated release of acetylcholine is probably caused by a reduced serotonergic tone on the inhibitory 5-HT1B heteroreceptors of the cholinergic terminals. When related to data in the literature, this facilitation may be of particular interest in terms of transmitter-based strategies developed to tackle cognitive symptoms related to neurodegenerative diseases. [source] Intrahippocampal administration of BDNF in adult rats affects short-term behavioral plasticity in the Morris water maze and performance in the elevated plus-mazeHIPPOCAMPUS, Issue 7 2004Francesca Cirulli Abstract The present study evaluated the effects of a single intrahippocampal administration of brain-derived neurotrophic factor (BDNF) on memory retention in a water maze. Adult rats were trained in a water maze (acquisition phase, day 1). Immediately after the last training trial subjects were injected in the right hippocampus with either BDNF (24 ,g) or phosphate-buffered saline (1 ,l). On day 2, all subjects were tested for memory retention in a probe trial and were subsequently tested for reversal learning. While no differences emerged in the probe trial, BDNF-treated subjects showed a shorter latency and a shorter path length to reach the platform during the reversal phase. A significant difference in their "turn angle" and in their swim paths suggests that they might have used a different search strategy compared with controls. Moreover, all subjects also underwent an elevated-plus maze test. BDNF-treated-animals showed a clear tendency to spend a greater amount of time in the open arms and a significantly higher frequency of grooming behavior and of the stretched-attend posture in this maze area, but no differences in locomotion. Overall, these results indicate that administration of BDNF improves performance in a spatial memory task and has enduring effects on emotional behavior. © 2004 Wiley-Liss, Inc. [source] Occurrence of oxidative impairments, response of antioxidant defences and associated biochemical perturbations in male reproductive milieu in the Streptozotocin-diabetic ratINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2007B. Shrilatha Summary Oxidative stress is implicated to play a vital role in the pathogenesis of various diabetic complications. While reproductive dysfunction is a well recognized consequence of diabetes mellitus, the underlying mechanisms are poorly understood. The present study aims to obtain insights into the incidence, extent and progression of oxidative impairments in testis and epididymal sperm (ES) in streptozotocin (STZ)-induced diabetic rat during early and progressive phase. Adult rats (CFT-Wistar strain) rendered diabetic by an acute dose of STZ (60 mg/kg bw, i.p.) were examined for induction of hyperglycaemia at 72 h, followed by the assessment of oxidative impairments in testis and ES over a 6-week period. Oxidative damage was ascertained by measuring the malondialdehyde levels, reactive oxygen species (ROS) generation, alterations in antioxidant defences and extent of protein oxidation. STZ induced a significant (2.5-fold) increase in blood glucose levels. In diabetic rats, both testis and ES showed enhanced status of lipid peroxidation measured as increased TBARS and ROS from week 2 onwards. These impairments in testis were consistent, progressive and accompanied by marked alterations in antioxidant defences and elevated protein carbonyls. Varying degree of reduction in the specific activities of antioxidant enzymes was evident in testis and ES, while the activity of glutathione- S -transferase (GST) was significantly elevated. Reduced glutathione (GSH) and vitamin E levels were consistently reduced in testis. Lipid dysmetabolism measured in terms of increased cholesterol, triglycerides and phospholipids was evident only beyond week 2 in diabetic testis. Taken together, these results indicate that the testis and ES are indeed subjected to significant oxidative stress in the STZ-diabetic rat both during early as well as progressive phase. It is hypothesized that oxidative impairments in testis which develop over time may at least in part contribute towards the development of testicular dysfunction eventually leading to testicular degeneration which culminates in reduced fertility during the progressive phase of STZ-induced diabetes in adult rats. [source] Noradrenergic depletion potentiates ,-amyloid induced cortical inflammation: implications for Alzheimer's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 2002D. L. Feinstein Degeneration of locus ceruleus (LC) neurons and reduced levels of noradrenaline (NA) in LC projection areas is a well known feature of Alzheimer's disease (AD); however, the consequences of those losses are not clear. Since inflammatory mediators contribute to AD pathogenesis, and since NA can suppress inflammatory gene expression, we tested if LC loss influenced brain inflammatory gene expression elicited by amyloid , (A,). Adult rats were injected with the selective neurotoxin DSP4 to induce LC death, and subsequently injected in cortex with A, (aggregated 1,42 peptide). DSP4-treatment potentiated the A,-dependent induction of inflammatory nitric oxide synthase (iNOS), IL-1, and IL6 expression compared to control animals. In contrast, the induction of cyclooxygenase-2 expression was not modified by DSP4-treatment. In control animals, injection of A, induced iNOS primarily in microglial cells, while in DSP4-treated animals iNOS was localized to neurons, as is observed in AD brains. Injection of A, increased IL-1, expression initially in microglia, and at later times in astrocytes, and expression levels were greater in DSP4 treated animals than controls. The potentiating effects of DSP4-treatment on iNOS and IL-1, expression were attenuated by coinjection with NA or the ,-adrenergic receptor agonist isoproterenol. These data demonstrate that LC loss and NA depletion augment inflammatory responses to A,, and suggest that LC loss in AD is permissive for increased inflammation and neuronal cell death. [source] Maternal Genotype Influences Stress Reactivity of Vasopressin-Deficient Brattleboro RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2003D. Zelena Abstract The role of vasopressin, cosecreted with corticotropin-releasing hormone (CRH), in stress is debated, because both normal as well as reduced adrenocorticotropin hormone (ACTH) rise to an acute challenge has been reported in Brattleboro rats genetically lacking vasopressin (di/di). Because di/di pups could be born either from di/+ (heterozygous) or from di/di mothers, and maternal influence is known to modify adult responsiveness, we investigated whether the influence of maternal genotype could explain the variability. Adult rats from mothers with different genotypes were stressed with 60 min restraint and trunk blood was collected for measuring hormone content by radioimmunoassay at the end of stress. All offspring of di/+ mothers had similar ACTH responses to restraint, while the di/di rats born to, and raised by di/di mothers showed reduced ACTH reactivity to restraint. The di/di rats showed elevated water turnover and required a daily cage cleaning every day, which meant frequent handling. To offset the role of handling, all rats had daily cage cleaning in the next series, but the results were the same as in the first series. To investigate whether lactation, the behaviour of the mother or some other factor during the pregnancy is responsible for the differences, pups from di/+ dams were raised by di/di foster mothers and vice versa. We found that the genotype of parental mother is more important than that of the foster mother. The corticosterone and prolactin elevation normally seen after acute stress was unchanged by family history, maternal or personal genotype. Furthermore, in studies with mutant animals, the rearing conditions should be controlled by the experimenter. In experiments with Brattleboro rats, the use of homozygous and heterozygous rats from the same litters of di/+ dams and di/di males is recommended. Our results suggest that vasopressin is not indispensable for ACTH release, and that the di/di genotype of the parental mother can decrease the stress reactivity of the di/di Brattleboro rats. [source] Effects of vibration treatment on tibial bone of ovariectomized rats analyzed by in vivo micro-CTJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2010Julienne E.M. Brouwers Abstract Daily low-amplitude, high-frequency whole-body vibration (WBV) treatment can increase bone formation rates and bone volume in rodents. Its effects vary, however, with vibration characteristics and study design, and effects on 3D bone microstructure of ovariectomized animals over time have not been documented. Our goal was to determine the effects of WBV on tibial bone of ovariectomized, mature rats over time using an in vivo micro-CT scanner. Adult rats were divided into: ovariectomy (OVX) (n,=,8), SHAM-OVX (n,=,8), OVX and WBV treatment (n,=,7). Eight weeks after OVX, rats in the vibration group were placed on a vibrating platform for 20,min at 0.3,g and 90 Hertz. This was done 5 days a week for six weeks, twice a day. Zero, 8, 10, 12 and 14 weeks after OVX, in vivo micro-CT scans were made (vivaCT 40, Scanco Medical AG) of the proximal and diaphyseal tibia. After sacrifice, all tibiae were dissected and tested in three-point bending. In the metaphysis between 8 to 12 weeks after OVX, WBV treatment did not alter structural parameters compared to the OVX group and both groups continued to show deterioration of bone structure. In the epiphysis, structural parameters were not altered. WBV also did not affect cortical bone and its bending properties. To summarize, no substantial effects of 6 weeks of low-magnitude, high-frequency vibration treatment on tibial bone microstructure and strength in ovariectomized rats were found. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:62,69, 2010 [source] Sensitization, Duration, and Pharmacological Blockade of Anxiety-Like Behavior Following Repeated Ethanol Withdrawal in Adolescent and Adult RatsALCOHOLISM, Issue 3 2009Tiffany A. Wills Background:, Repeated ethanol withdrawal sensitizes anxiety-like behavior in adult rats and causes anxiety-like behavior and decreased seizure thresholds in adolescent rats. Current experiments determined if adolescent rats exhibit sensitized anxiety-like behavior, the duration of this effect, if drug pretreatments blocked these effects, and if these effects differed from those seen in adults. Methods:, Male adolescent rats received three 5-day cycles of 2.5% ethanol diet (ED) separated by two 2-day withdrawal periods, continuous 15 days of 2.5%ED, or a single 5-day cycle of 2.5%ED. Male adult rats received three 5-day cycles of either 2.5% or 3.5%ED. These groups were tested 5 hours into the final withdrawal for social interaction (SI) deficits (an index of anxiety-like behavior). Ethanol intake was monitored throughout and blood concentrations were obtained from separate groups of rats. Additionally, adolescent rats were tested for SI 1, 2, 7, 14, and 18 days and adults 1 and 2 days after the final withdrawal. Some adolescent rats were also pretreated with the CRF1 antagonist CP-154,526, the 5-HT1A agonist buspirone, or the benzodiazepine receptor antagonist flumazenil during the first 2 withdrawals. Results:, SI was reduced in adolescent rats following repeated withdrawals of 2.5%ED while neither a continuous or single cycle ED exposure caused this effect. Adult rats also had reduced SI following repeated withdrawals from both 2.5% and 3.5%ED. This effect was present up to 1 week following the final withdrawal in adolescents but returned to baseline by 1 day in adults. CP-154,526, buspirone, or flumazenil prevented this reduction in SI in adolescent rats. Conclusions:, Adolescent rats exhibit sensitized anxiety-like behavior following repeated withdrawals at ED concentrations similar to those used in adults. However, this effect is longer lasting in adolescent rats. Drugs modulating CRF, 5-HT, or GABA systems during initial withdrawals prevent the development of anxiety-like behavior otherwise manifest during a final withdrawal in adolescent rats. [source] Differential Dietary Ethanol Intake and Blood Ethanol Levels in Adolescent and Adult Rats: Effects on Anxiety-Like Behavior and Seizure ThresholdsALCOHOLISM, Issue 8 2008Tiffany A. Wills Background:, Adult rats exhibit increased anxiety-like behavior after exposure to repeated cycles of chronic ethanol and withdrawal. While adolescent rats have differential responses to both acute and chronic ethanol treatments, the potential differences in the effects of repeated withdrawals in this population have yet to be determined. Methods:, Male adult and adolescent rats received three 5-day cycles of either a 4.5% or 7% ethanol diet (ED) separated by two 2-day withdrawal periods. Five hours into the final withdrawal, rats were tested for social interaction (SI) deficits (an index of anxiety-like behavior) and then assessed for seizure thresholds (audiogenic and bicuculline-induced). Ethanol intake was monitored throughout, and blood ethanol concentrations (BEC) were obtained from a separate group of rats. Results:, Adolescent rats have reduced SI during the final withdrawal from either ED and exhibit a greater reduction in SI compared to adult rats when exposed to a 7%ED. Audiogenic seizures were not increased during withdrawal from either ED in adult rats, but adolescent rats that received 7%ED displayed increased seizures. The bicuculline seizure thresholds were decreased in both ages exposed to a 7%ED, but only adolescent rats showed this decreased threshold after 4.5%ED. Ethanol intakes and BECs were higher in adolescent rats compared to similarly treated adults. However, ethanol intakes and BECs were comparable between 4.5%ED-treated adolescent and 7%ED-treated adult rats. Conclusions:, Behavioral results from the 7%ED-treated groups suggested that adolescent rats may be more vulnerable to repeated withdrawals from ethanol than adults; however, differences in ethanol intake and BECs may be at least in part responsible. When ethanol intakes and BECs were similar between 4.5%ED-treated adolescent and 7%ED-treated adult rats, behavioral effects were not different. Importantly, these data illustrated that adolescent rats can exhibit anxiety and reduced seizure thresholds following this repeated withdrawal paradigm. [source] Systemic steroid reduces long-term hearing loss in experimental pneumococcal meningitis,THE LARYNGOSCOPE, Issue 9 2010Lise Worsøe MD Abstract Objectives/Hypothesis: Sensorineural hearing loss is a common complication of pneumococcal meningitis. Treatment with corticosteroids reduces inflammatory response and may thereby reduce hearing loss. However, both experimental studies and clinical trials investigating the effect of corticosteroids on hearing loss have generated conflicting results. The objective of the present study was to determine whether systemic steroid treatment had an effect on hearing loss and cochlear damage in a rat model of pneumococcal meningitis. Study Design: Controlled animal study of acute bacterial meningitis. Methods: Adult rats were randomly assigned to two experimental treatment groups: a group treated with systemic steroid (n = 13) and a control group treated with saline (n = 13). Treatment was initiated 21 hours after infection and repeated once a day for three days. Hearing loss and cochlear damage were assessed by distortion product otoacoustic emissions (DPOAE), auditory brainstem response (ABR) at 16 kHz, and spiral ganglion neuron density. Results: Fifty-six days after infection, steroid treatment significantly reduced hearing loss assessed by DPOAE (P < .05; Mann-Whitney) and showed a trend toward reducing loss of viable neurons in the spiral ganglion (P = .0513; Mann-Whitney). After pooling data from day 22 with data from day 56, we found that systemic steroid treatment significantly reduced loss of spiral ganglion neurons (P = .0098; Mann-Whitney test). Conclusions: Systemic steroid treatment reduces long-term hearing loss and loss of spiral ganglion neurons in experimental pneumococcal meningitis in adult rats. The findings support a beneficial role of anti-inflammatory agents in reducing hearing loss and cochlear damage in meningitis. Laryngoscope, 2010 [source] Delayed treatment with a p53 inhibitor enhances recovery in stroke brain,ANNALS OF NEUROLOGY, Issue 5 2009Yu Luo PhD Objective Cerebral ischemia can activate endogenous reparative processes, such as proliferation of endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ). Most of these new cells die shortly after injury. The purpose of this study was to examine a novel strategy for treatment of stroke at 1 week after injury by enhancing the survival of ischemia-induced endogenous NPCs in SVZ. Methods Adult rats were subjected to a 90-minutes middle cerebral artery occlusion. A p53 inhibitor pifithrin-, (PFT-,) was administered to stroke rats from days 6 to 9 after middle cerebral artery occlusion. Locomotor behavior was measured using an activity chamber. Proliferation, survival, migration, and differentiation of endogenous NPCs were examined using quantitative reverse transcription polymerase chain reaction, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, and immunohistochemistry. Results PFT-, enhanced functional recovery as assessed by a significant increase in multiple behavioral measurements. Delayed PFT-, treatment had no effect on the cell death processes in the lesioned cortical region. However, it enhanced the survival of SVZ progenitor cells, and promoted their proliferation and migration. PFT-, inhibited the expression of a p53-dependent proapoptotic gene, termed PUMA (p53-upregulated modulator of apoptosis), within the SVZ of stroke animals. The enhancement of survival/proliferation of NPCs was further found in SVZ neurospheres in tissue culture. PFT-, dose-dependently increased the number and size of new neurosphere formation. Interpretation Delayed treatment with a p53 inhibitor PFT-, is able to modify stroke-induced endogenous neurogenesis and improve the functional recovery in stroke animals. Ann Neurol 2009;65:520,530 [source] Ontogeny of urine preference and its relationship to NH4Cl preference and sodium hunger in suckling rat pupsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2005Micah Leshem Abstract We chart the postnatal ontogeny of urine preference in the suckling rat. Twelve-day-old sucklings, when offered urine, NH4Cl, or NaCl, ingest more urine and NH4Cl than NaCl. When rendered sodium hungry by ivc renin or by sodium depletion, these sucklings prefer urine and NH4Cl to NaCl, dilute urine, or an NaCl and KCl mineral mix equimolar to urine; however, by 18 days of age, urine and NH4Cl are no longer preferred to NaCl. Hence, urine preference in the suckling may be specific and preparatory for the variety of purposes urine preference serves in the adult rat, and it might guide the pup to urinary sodium in the nest. Since preference for urine and NH4Cl covary during postnatal development, the high preference for NH4Cl in midterm sucklings might be because its ammonium flavor is similar to urine. © 2005 Wiley Periodicals, Inc. Dev Psychobiol 46: 111,117, 2005. [source] Study by transmission and scanning electron microscopy of the morphogenesis of three types of lingual papillae in the albino rat (Rattus rattus)ACTA ZOOLOGICA, Issue 3 2010Ahlam Mostafa El-Bakry Abstract El-Bakry, A.M. 2010. Study by transmission and scanning electron microscopy of the morphogenesis of three types of lingual papillae in the albino rat (Rattus rattus).,Acta Zoologica (Stockholm) 91: 267,278 Tongues were removed from albino rat foetus on days 12 (E12) and 16 (E16) of gestation and from newborns (P0) and from juvenile rats on days 7 (P7), 14 (P14) and 21 (P21) postnatally for investigation by light, scanning, and transmission electron microscopy. Significant changes appeared during the morphogenesis of the papillae. At E12, two rows of rudiments of fungiform papillae were extended bilaterally on the anterior half of the tongue. At E16, the rudiments of fungiform papillae were regularly arranged in a lattice-like pattern. A rudiment of circumvallate papillae could be recognized. No rudiment of filiform papillae was visible. No evidence of keratinization was recognizable. At P0, rudiments of filiform papillae were visible but had a more rounded appearance, with keratinization. The fungiform and circumvallate papillae were large and their outlines were somewhat irregular as that found in the adult rat. At P7, the filiform papillae were large and slender. The fungiform papillae became large and the shape of circumvallate papillae was almost similar to that observed in the adult. At P14 and P21, the shape and structure of the three types of papillae were irregular as those found in the adult. In conclusion, the rudiments of the fungiform and circumvallate papillae were visible earlier than those of the filiform papillae. The morphogenesis of filiform papillae advanced in a parallel manner with the keratinization of the lingual epithelium, in the period from just before birth to a few weeks after birth. [source] The nitric oxide/cyclic guanosine monophosphate pathway modulates the inspiratory-related activity of hypoglossal motoneurons in the adult ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2008Fernando Montero Abstract Motoneurons integrate interneuronal activity into commands for skeletal muscle contraction and relaxation to perform motor actions. Hypoglossal motoneurons (HMNs) are involved in essential motor functions such as breathing, mastication, swallowing and phonation. We have investigated the role of the gaseous molecule nitric oxide (NO) in the regulation of the inspiratory-related activity of HMNs in order to further understand how neural activity is transformed into motor activity. In adult rats, we observed nitrergic fibers and bouton-like structures in close proximity to motoneurons, which normally lack the molecular machinery to synthesize NO. In addition, immunohistochemistry studies demonstrated that perfusion of animals with a NO donor resulted in an increase in the levels of cyclic guanosine monophosphate (cGMP) in motoneurons, which express the soluble guanylyl cyclase (sGC) in the hypoglossal nucleus. Modulators of the NO/cGMP pathway were micro-iontophoretically applied while performing single-unit extracellular recordings in the adult decerebrated rat. Application of a NO synthase inhibitor or a sGC inhibitor induced a statistically significant reduction in the inspiratory-related activity of HMNs. However, excitatory effects were observed by ejection of a NO donor or a cell-permeable analogue of cGMP. In slice preparations, application to the bath of a NO donor evoked membrane depolarization and a decrease in rheobase, which were prevented by co-addition to the bath of a sGC inhibitor. These effects were not prevented by reduction of the spontaneous synaptic activity. We conclude that NO from afferent fibers anterogradely modulates the inspiratory-related activity of HMNs by a cGMP-dependent mechanism in physiological conditions. [source] Differentiation and migration of astrocytes in the spinal cord following dorsal root injury in the adult ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2003Elena N. Kozlova Abstract Nerve fibre degeneration in the spinal cord is accompanied by astroglial proliferation. It is not known whether these cells proliferate in situ or are recruited from specific regions harbouring astroglial precursors. We found cells expressing nestin, characteristic of astroglial precursors, at the dorsal surface of the spinal cord on the operated side from 30 h after dorsal root injury. Nestin-expressing cells dispersed to deeper areas of the dorsal funiculus and dorsal horn on the operated side during the first few days after injury. Injection of bromodeoxyuridine (BrdU) 2 h before the end of the experiment, at 30 h after injury, revealed numerous BrdU-labelled, nestin-positive cells in the dorsal superficial region. In animals surviving 20 h after BrdU injection at 28 h postlesion, cells double-labelled with BrdU and nestin were also found in deeper areas. Labeling with BrdU 2 h before perfusion showed proliferation of microglia and radial astrocytes in the ventral and lateral funiculi on both sides of the spinal cord 30 h after injury. Nestin-positive cells coexpressed the calcium-binding protein Mts1, a marker for white matter astrocytes, in the dorsal funiculus, and were positive for glial fibrillary acidic protein (GFAP), but negative for Mts1 in the dorsal horn. One week after injury the level of nestin expression decreased and was undetectable after 3 months. Taken together, our data indicate that after dorsal root injury newly formed astrocytes in the degenerating white and grey matter first appear at the dorsal surface of the spinal cord from where some of them subsequently migrate ventrally, and differentiate into white- or grey-matter astrocytes. [source] Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2003Manel M. Santafé Abstract We studied the presynaptic muscarinic autoreceptor subtypes controlling ACh release and their relationship with voltage-dependent calcium channels in the neuromuscular synapses of the Levator auris longus muscle from adult (30,40 days) and newborn (3,6 and 15 days postnatal) rats. Using intracellular recording, we studied how several muscarinic antagonists affected the evoked endplate potentials. In some experiments we previously incubated the muscle with calcium channel blockers (nitrendipine, ,-conotoxin-GVIA and ,-Agatoxin-IVA) before determining the muscarinic response. In the adult, the M1 receptor-selective antagonist pirenzepine (10 µm) reduced evoked neurotransmission (, 47%). The M2 receptor-selective antagonist methoctramine (1 µm) increased the evoked release (, 67%). Both M1- and M2-mediated mechanisms depend on calcium influx via P/Q-type synaptic channels. We found nothing to indicate the presence of M3 (4-DAMP-sensitive) or M4 (tropicamide-sensitive) receptors in the muscles of adult or newborn rats. In the 3,6-day newborn rats, pirenzepine reduced the evoked release (, 30%) by a mechanism independent of L-, N- and P/Q-type calcium channels, and the M2 antagonist methoctramine (1 µm) unexpectedly decreased the evoked release (, 40%). This methoctramine effect was a P/Q-type calcium-channel-dependent mechanism. However, upon maturation in the first two postnatal weeks, the M2 pathway shifted to perform the calcium-dependent release-inhibitory activity found in the adult. We show that the way in which M1 and M2 muscarinic receptors modulate neurotransmission can differ between the developing and adult rat neuromuscular synapse. [source] Comparative distribution of the mammalian mediator subunit thyroid hormone receptor-associated protein (TRAP220) mRNA in developing and adult rodent brainEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2002Anastasia Galeeva Abstract TRAP220 (thyroid hormone receptor-associated protein) is a recently cloned nuclear receptor coactivator, which interacts with several nuclear receptors in a ligand-dependent manner and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. TRAP220 has been shown to interact with thyroid hormone receptors, vitamin D receptors, peroxisome proliferator-activated receptors, retinoic acid receptors and oestrogen receptors. Thyroid hormone and retinoic acid play very important roles in brain development and they also influence adult brain. Using in situ hybridization we have examined expression of TRAP220 mRNA in the central nervous system during development and in adult rat and mouse brain. Expression of TRAP220 was seen already during early embryonic development in the epithelium of neural tube at E9 in mouse and at E12 in rat. At later stages of development the strongest signal was seen in different layers of cerebral neocortex, external germinal layer of cerebellum, differentiating fields of hippocampus and neuroepithelium, and a moderate signal was detected in basal ganglia, different areas of diencephalon and midbrain. In adult rat brain the signal was more restricted than during development. TRAP220 expression occurred mostly in the granular layer of cerebellar cortex, piriform cortex and hippocampal formation. The signal was found predominantly in neurons. Our work supports the assumption that TRAP220 plays an important role in growth and differentiation of central nervous system and may have a function in certain areas of adult brain. [source] Expression of ephrin-A2 in the superior colliculus and EphA5 in the retina following optic nerve section in adult ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2001J. Rodger Abstract The vertebrate retina projects topographically to visual brain centres. In the developing visual system, gradients of ephrins and Eph receptors play a role in defining topography. At maturity, ephrins but not Ephs are downregulated. Here we show that optic nerve section in adult rat differentially regulates the expression of ephrin-A2 in the superior colliculus (SC) and of EphA5 in the retina. Expression was quantified immunohistochemically; ephrin-A2 levels were also estimated by semiquantitative reverse transcriptase polymerase chain reaction. In the normal SC, ephrin-A2 was expressed at low levels. At 1 month, levels of protein and of mRNA were upregulated across the contralateral SC giving rise to an increasing rostro-caudal gradient. At 6 months, levels had fallen but a gradient remained. In the retina of normal animals, EphA5 was expressed as an increasing naso-temporal gradient. By 1 month, expression was decreased in far temporal retina, resulting in a uniform expression across the naso-temporal axis. We suggest that denervation-induced plastic changes within the SC modify expression of these molecules. [source] Injury induced c-Jun expression and phosphorylation in the dopaminergic nigral neurons of the rat: correlation with neuronal death and modulation by glial-cell-line-derived neurotrophic factorEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2001Elisabetta Vaudano Abstract This study was designed to determine whether induction and phosphorylation of the transcription factor c-Jun is associated with lesion-induced death of dopaminergic neurons of the substantia nigra pars compacta, and if this cellular response is modulated by glial-cell-line-derived neurotrophic factor. In adult rats, delayed dopaminergic neuron cell death induced by intrastriatal 6-hydroxydopamine injection led to a marked increase in the number of both c-Jun- and phosphorylated c-Jun-immunoreactive nuclei in the substantia nigra pars compacta. The response was maximal before any significant loss of nigral neurons could be detected (on day 7 post lesion) and was confined to the dopaminergic neurons. Similarly, 6-hydroxydopamine lesion of the striatal dopaminergic terminals or excitotoxic lesion of the striatal target neurons in neonatal rats resulted in an increased number of c-Jun- and phosphorylated c-Jun-immunoreactive nigral nuclei that preceded the loss of nigral dopaminergic neurons. By contrast, after an excitotoxic lesion of the striatal target neurons in the adult rat, resulting in atrophy but not cell death of the nigral dopaminergic neurons, no upregulation of either c-Jun or phosphorylated c-Jun was found. A single injection of 10 µg of glial-cell-line-derived-neurotrophic factor given at day 3 after the intrastriatal 6-hydroxydopamine lesion reduced the number of c-Jun- and phosphorylated c-Jun-immunoreactive nuclei in the substantia nigra and protected the dopaminergic neurons from the ensuing cell death. We conclude that c-Jun induction and phosphorylation may be involved in the cellular events leading to death of nigral dopaminergic neurons in vivo and that this response can be modulated by glial-cell-line-derived-neurotrophic factor. [source] | ||||||||||||||||||||||||||||||||||