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Rat Pups (rat + pup)
Kinds of Rat Pups Selected AbstractsPentylenetetrazol-induced Recurrent Seizures in Rat Pups: Time Course on Spatial Learning and Long-term EffectsEPILEPSIA, Issue 6 2002Li-Tung Huang Summary: ,Purpose: Recurrent seizures in infants are associated with a high incidence of neurocognitive deficits. Animal models have suggested that the immature brain is less vulnerable to seizure-induced injury than is that in adult animals. We studied the effects of recurrent neonatal seizures on cognitive tasks performed when the animals were in adolescence and adulthood. Methods: Seizures were induced by intraperitoneal injection of pentylenetetrazol (PTZ) for 5 consecutive days, starting from postnatal day 10 (P10). At P35 and P60, rats were tested for spatial memory by using the Morris water maze task. In adulthood, motor performance was examined by the Rotarod test, and activity level was assessed by the open field test. Seizure threshold was examined by inhalant flurothyl. To assess presence or absence of spontaneous seizures, rats were video recorded for 4 h/day for 10 consecutive days for the detection of spontaneous seizures. Finally, brains were examined for histologic evidence of injury with cresyl violet stain and Timm staining in the supragranular zone and CA3 pyramidal cell layers of the hippocampus. Results: PTZ-treated rats showed significant spatial deficits in the Morris water maze at both P35 and P60. There were no differences in seizure threshold, motor balance, or activity level during the open field test. Spontaneous seizures were not recorded in any rat. The cresyl violet stain showed no cell loss in either the control or experimental rats. PTZ-treated rats exhibited more Timm staining in the CA3 subfield. However, the control and experimental rats showed similar Timm staining within the supragranular zone. Conclusions: Our findings indicate that recurrent PTZ-induced seizures result in long-term cognitive deficits and morphologic changes in the developing brain. Furthermore, these cognitive deficits could be detected during pubescence. [source] Eyeblink conditioning using cochlear nucleus stimulation as a conditioned stimulus in developing ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 7 2008John H. Freeman Abstract Previous studies demonstrated that the development of auditory conditioned stimulus (CS) input to the cerebellum may be a neural mechanism underlying the ontogenetic emergence of eyeblink conditioning in rats. The current study investigated the role of developmental changes in the projections of the cochlear nucleus (CN) in the ontogeny of eyeblink conditioning using electrical stimulation of the CN as a CS. Rat pups were implanted with a bipolar stimulating electrode in the CN and given six 100-trial training sessions with a 300 ms stimulation train in the CN paired with a 10 ms periorbital shock unconditioned stimulus (US) on postnatal days (P) 17,18 or 24,25. Control groups were given unpaired presentations of the CS and US. Rats in both age groups that received paired training showed significant increases in eyeblink conditioned responses across training relative to the unpaired groups. The rats trained on P24,25, however, showed stronger conditioning relative to the group trained on P17,18. Rats with missed electrodes in the inferior cerebellar peduncle or in the cerebellar cortex did not show conditioning. The findings suggest that developmental changes in the CN projections to the pons, inferior colliculus, or medial auditory thalamus may be a neural mechanism underlying the ontogeny of auditory eyeblink conditioning. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 640-646, 2008. [source] Effects of neonatal handling and maternal separation on rough-and-tumble play in the ratDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2002Jennifer L. Arnold Abstract The extent to which brief daily handling and longer periods of separation from the mother during the first 2 weeks of life can affect play behavior in juvenile rats was assessed. Rat pups were separated from the mother for either 15 min daily (handling) or for 3 hr daily (maternal separation), and play was observed as juveniles. Overall levels of playfulness were not affected by either manipulation, although certain aspects of playful responsiveness were affected in males, but not females. In particular, the pattern of responsiveness to playful contacts was feminized in both handled and separated male rats. Activity in a novel open field at 15 days of age was increased in both males and females from the separated group, but not in the handled animals, as were the number of rears exhibited during the play bouts. These data suggest that early rearing experiences can have subtle gender-dependent effects on some aspects of play in juvenile rats and that the underlying mechanism(s) responsible for these effects may differ from those associated with other effects reported for handling and maternal separation. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 41: 205,215, 2002. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/dev.10069 [source] Role of cortical dysplasia in epileptogenesis following prolonged febrile seizureEPILEPSIA, Issue 9 2010Kyung-Il Park Summary Purpose:, Hippocampal sclerosis, characterized by prominent neuronal loss and reactive gliosis, is the most common pathology in human temporal lobe epilepsy (TLE). Although prolonged febrile convulsion (FC) is a risk factor of TLE, it is not clear whether FC provokes hippocampal sclerosis and subsequent TLE. Given that underlying brain lesions, such as cortical dysplasia (CD), in the immature brain predispose patients to FC, CD may link FC and TLE. However, the role of CD in epileptogenesis after FC is also unclear. Here, we investigated whether inborn CD increases the risk of later epilepsy induced by prolonged FC using a rat model. Methods:, Experimental CD was induced by in utero exposure of methylazoxymethanol (MAM). Rat pups from MAM-treated or control rats were then subjected to prolonged FC. We examined morphologic changes in the hippocampi with respect to neuronal loss, reactive gliosis, and synaptogenesis, and evaluated spontaneous recurrent seizures (SRS) by long-term video-EEG (electroencephalography). Results:, The MAM+FC group had a significantly lower hippocampal neuronal density in the CA1 and dentate hilus than other control groups. A robust increase in glial cells and synaptic reorganization was also detected in the MAM+FC groups. Furthermore, later SRS occurred in all rats in the MAM+FC group and in 50% and 25% of the rats in the FC-only and MAM-only group, respectively. The frequency and total duration of SRS was highest in the MAM+FC group. Discussion:, Our results suggest that preexisting CD in the immature brain augments the proepileptogenic effects of prolonged FC, leading to TLE. [source] The ontogeny of postingestive inhibitory stimuli: Examining the role of CCKDEVELOPMENTAL PSYCHOBIOLOGY, Issue 5 2006Aron Weller Abstract Cholecystokinin (CCK) inhibits food intake in adults. This paper describes research examining the ability of CCK to affect feeding in infant rats and the role of CCK in the developmentally emerging ability of the rat pup to inhibit ingestion in response to sensory characteristics of food. First, data will be described from studies that asked if the CCK system is functional in preweanling rats. Specifically, these studies examined whether exogenous and endogenous CCK can decrease intake of the infant rat during independent ingestion (of a milk diet, away from the dam). In addition, the ability of exogenous CCK to activate central feeding-control areas in the brain stem and hypothalamus in infant rats was examined by C-FOS staining. Next, experiments examining which specific intake-inhibitory sensory aspects of food are mediated by CCK will be described. The volume, hypertonicity, fat, carbohydrate and protein content of a preload were separately manipulated in different studies, followed closely by a 30-min test meal. The selective CCK1 receptor antagonist devazepide was used to assess CCK mediation of the control of intake produced by particular sensory aspects of food, at the earliest age in which this ability to control intake appears. Finally, the pattern of independent ingestion in infant OLETF rats lacking CCK1 receptors was examined. The results suggest that the CCK intake-inhibitory mechanism is potentially available to the young, suckling pup even before it starts to feed on its own. However, it appears to mediate only a portion of the controls of intake during nursing and early stages of weaning. Some aspects of the CCK system (e.g., forebrain-hindbrain connections) and CCK's role in mediating the effects of other stimulus aspects of food apparently undergo a post-weaning maturational process. © 2006 Wiley Periodicals, Inc. Dev Psychobiol 48: 368,379, 2006. [source] Long maternal separation has protective effects in rats exposed to activity-based anorexiaDEVELOPMENTAL PSYCHOBIOLOGY, Issue 8 2009O. Carrera Abstract This study examined the effect of three neonatal treatments of maternal separation during infancy in young adult rats exposed to standard activity-based anorexia (ABA) consisting of food restriction plus free access to an activity wheel. During the first 20 postnatal days of life rat pups were exposed to periods of either brief maternal separation (BMS, 15,min), long maternal separation (LMS, 180,min), or were non-handled (NH). Thereafter, male and female rats were exposed to ABA. Neonatal treatment produced no significant differences in the survival time of male rats, whereas survival was greater in female rats exposed to LMS than in NH rats under ABA procedure. In conclusion, prolonged maternal separation appears to promote resistance in female animals subjected to harsh ABA life-threatening conditions. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 616,624, 2009 [source] Rats selectively bred for low levels of 50 kHz ultrasonic vocalizations exhibit alterations in early social motivationDEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2008K.M. Harmon Abstract In rats, the rates of 50 kHz ultrasonic vocalizations (USVs) can be used as a selective breeding phenotype and variations in this phenotype can be an indicator of affective states. The 50 kHz USV is elicited by rewarding stimuli (e.g., food, sexual behavior) and therefore can express a positive affective state. Conversely, the 22 kHz USV is elicited by aversive stimuli (e.g., presence of a predator, social defeat) indicating a negative affective state. In the present study, we tested the effect of selectively breeding for 50 kHz USVs on a variety of maternal social/emotional behaviors in young rat pups (PND 10-12). These measures consisted of an assessment of isolation calls and conditioned odor preference paradigm. Results indicate that animals selected for low levels of 50 kHz USVs show the greatest alterations in social behaviors compared to the control animals. The low line animals had an increase in isolation calls tested during place preference conditioning and a decrease in 50 kHz ultrasonic calls in all conditions. These same low line animals failed to show a typical preference for a maternally-associated odor during the place preference test. The different social behaviors of the high line animals did not consistently vary from those of the control group. These results have important implications for the study of genetic and epigenetic mechanisms underlying emotional states, and possibly contribute to the research underlying the emotional changes in developmental disorders such as autistic spectrum disorder by providing a novel animal model that displays communication deficits that are interdependent with significant social behavioral impairments. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 322,331, 2008. [source] Rapid acquisition of operant conditioning in 5-day-old rat pups: A new technique articulating suckling-related motor activity and milk reinforcementDEVELOPMENTAL PSYCHOBIOLOGY, Issue 6 2007Carlos Arias Abstract Newborn rats are capable of obtaining milk by attaching to a surrogate nipple. During this procedure pups show a gradual increase in head and forelimb movements oriented towards the artificial device that are similar to those observed during nipple attachment. In the present study the probability of execution of these behaviors was analyzed as a function of their contingency with intraoral milk infusion using brief training procedures (15 min). Five-day-old pups were positioned in a smooth surface having access to a touch-sensitive sensor. Physical contact with the sensor activated an infusion pump which served to deliver intraoral milk reinforcement (Paired group). Yoked controls received the reinforcer when Paired neonates touched the sensor. Paired pups trained under a continuous reinforcement schedule emitted significantly more responses than Yoked controls following two (Experiment 1) or one training session (Experiment 2). These differences were also observed during an extinction session conducted immediately after training. The level of maternal deprivation before training (3 or 6 hr) or the volume of milk delivered (1.0 or 1.5 µl per pulse) did not affect acquisition or extinction performances. In addition, it was observed that the rate of responding of Paired pups during the early phase of the extinction session significantly predicted subsequent levels of acceptance of the reinforcer. These results indicate that the frequency of suckling-related behaviors can be rapidly modified by means of associative operant processes. The operant procedure here described represents an alternative tool for the ontogenetic analysis of self-administration or behavior processes of seeking. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 576-588, 2007. [source] Early weaning decreases play-fighting behavior during the postweaning developmental period of wistar ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2007Michito Shimozuru Abstract We examined the influence of early weaning on the development of play-fighting behaviors and anxiety status in Wistar rats. Pups were divided into two groups, those weaned at postnatal day (PD) 16 (early-weaned group) and those weaned at PD30 (normally weaned group), and were housed in pairs of the same sex. Playful interactions were measured for each pair once a week from 4 to 7 weeks of age. Thereafter, during early adulthood, all the rats were subjected to the elevated plus-maze test. The frequencies of pinning and playful attack were less in the early-weaned group than in the normally weaned group. In the elevated plus-maze test, rat pups in the early-weaned group had higher anxiety levels. The results showed that deprivation of mother,pup interactions during the preweaning period decreases affiliative interactions between cage mates, including play-fighting behaviors during the postweaning developmental period, and increases anxiety levels during early adulthood. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 343,350, 2007. [source] Effects of neonatal novelty exposure on sexual behavior, fear, and stress-response in adult ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2007Fernando Benetti Abstract Environmental stimuli in early life may result in permanent behavioral and physiological changes. Present study evaluated the effects of exposing pups to a novel environment on behaviors (open-field test and sexual behavior) and prolactin stress-responses in adult male rats. Half of a litter was daily removed outside (OUT) from the nest and stimulated by handling for 3 min, while the other half remained inside (IN) the nest and was also handled for the same period during the first 10 days postpartum. Maternal behavior after all the pups were returned to the nest was not different between IN and OUT littermates. In adulthood, OUT males showed increased general and central locomotion activity in the open-field test, reduced sexual behavior, and attenuated prolactin secretion in response to restraint stress compared with the IN littermates. The repeated exposition of rat pups to a novel environment is a causal factor for the long-lasting behavioral and endocrine changes. The premature exposition of the pup to unfamiliar environments decreases fear and stress-response, and also reduces sexual behavior. We suggest that the absence of the odor of the mother may be crucial to explain the effects detected in adulthood. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 258,264, 2007. [source] Brief exposure to the biological mother "potentiates" the isolation behavior of precocial Guinea pig pupsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 8 2006Michael B. Hennessy Abstract When isolated rat pups are briefly reunited with a lactating female, her subsequent removal leads to a dramatic increase in the emission of ultrasonic vocalizations, but not other behaviors. Whether this socially induced augmentation of isolation behavior (i.e., "potentiation") is characteristic only of altricial rodents is not known. Therefore, we examined precocial guinea pig pups in a potentiation paradigm. Ten-day-old guinea pigs were isolated in a test cage for 10 min, at which time they were then placed into a second cage for 5 min that either contained a companion or, for controls, was empty. Pups were then isolated again in the test cage for a second 10-min period. Control pups showed a significant reduction in vocalizing and locomotor activity from the first to second isolation period. Exposure to the biological mother prevented the decline in both behaviors (Experiment 1), whereas exposure to a familiar littermate (Experiment 2) had no effect, and exposure to an unfamiliar lactating female (Experiment 3) had only a minimal effect on locomotor activity. The results show that potentiation of isolation behaviors is not limited to altricial rodents, and suggest that specific characteristics of the effect (i.e., its magnitude, the specific behaviors affected, and the selectivity of the response to particular social partners) varies with the abilities and requirements of the young, as well as the behavioral ecology of the species in question. © 2006 Wiley Periodicals, Inc. Dev Psychobiol 48: 653,659, 2006. [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] Maternal memory in adult, nulliparous rats: Effects of testing interval on the retention of maternal behaviorDEVELOPMENTAL PSYCHOBIOLOGY, Issue 1 2005Robert S. Bridges Abstract The retention of maternal behavior (i.e., maternal memory) was measured in adult, nulliparous rats induced to respond maternally by continuous exposure to foster pups. Specifically, the effects of the interval duration between the initial induction and the reinduction of maternal behavior were determined. Intact virgin rats were first exposed to foster young to induce maternal behavior. During the initial induction phase, females were required to be fully maternal on 2 consecutive test days. Animals were then assigned to one of three interval groups (10, 20, or 40 days). After being isolated from rat pups for these designated periods, females in each group were tested again for their latencies to induce maternal behavior. Whereas the initial median latencies to display full maternal behavior ranged from 4.5 to 5 days for each group, upon retesting, median latencies for each group declined to 1 to 4 days. The greatest reduction in latency was present in the 10-day group (80%), and the smallest reduction was detected in the 40-day group (20%). A significant negative linear correlation was found between test interval and percentage reduction in behavioral latency. Based upon this relationship and under these test conditions, "maternal memory" in the adult, nulliparous rat would be expected to be nondetectable after about an interval of 50 days between tests. The pattern of maternal memory acquisition and loss appears similar to that reported in parous animals. The present study highlights similarities and possible differences underlying the establishment of the retention of maternal behavior (i.e., maternal memory). © 2004 Wiley Periodicals, Inc. Dev Psychobiol 46: 13,18, 2005. [source] Distinct caspase pathways mediate necrosis and apoptosis in subpopulations of hippocampal neurons after status epilepticusEPILEPSIA, Issue 2010Maria-Leonor Lopez-Meraz Summary Status epilepticus in the immature brain induces neuronal injury in the hippocampal formation, but the mode and mechanism of death are poorly understood. Our laboratory has recently investigated the role of caspase-3, -8, and -9 in neuronal injury, using a lithium,pilocarpine model of status epilepticus in 2-week-old rat pups. Our results showed that dying neurons in the dentate gyrus and CA1-subiculum area do not share the same mechanism of death. In CA1-subiculum, caspase-8 upregulation preceded caspase-3 activation in morphologically necrotic neurons. The pan-caspase inhibitor Q-VD-OPH reduced CA1 damage, showing that caspases contribute to status epilepticus,induced necrosis. In the dentate gyrus, dying neurons were caspase-9 and -3 immunoreactive and morphologically apoptotic. It is not clear why the same seizures cause different types of cell death in neurons that are connected in series along the same hippocampal circuit, but the apoptotic dentate neurons express doublecortin, and do not express calbindin-D28k, suggesting that their immaturity may be a factor in producing an apoptotic mode of death. [source] Anticonvulsant Action of Topiramate Against Motor Seizures in Developing RatsEPILEPSIA, Issue 10 2000Renata Haugvicová Summary Purpose: To study the anticonvulsant action of topiramate (TPM) in developing rats. Methods: Motor seizures were elicited by administering pentylenetetrazol (100 mg/kg subcutaneously) in five age groups of Wistar rats (7, 12, 18, 25, and 90 days old). TPM was administered intraperitoneally in doses from 10 to 640 mg/kg 2 hours before pentylenetetrazol. The time course of TPM action was studied in 12- and 25-day-oId rats up to 24 hours after the 160-mg/kg dose, and the incidence and pattern of seizures were evaluated. Results: TPM did not influence minimal seizures (clonus of forelimb and head muscles with preserved righting ability). Generalized tonic-clonic seizures, however, were reliably changed at all developmental stages studied. The tonic phase was suppressed so that the majority of animals exhibited generalized clonic seizures (with a loss of righting reflexes). In addition, the incidence of generalized seizures was decreased after the 20-, 40-, and 80-mg/kg doses in the 7-day-old rat pups. The specific suppression of the tonic phase of generalized seizures was observed up to 12 hours in the 12-day-old rat pups. The same result was obtained over 6 hours after TPM administration in the 25-day-old animals, and with longer intervals the incidence of generalized seizures decreased in this age group. Conclusions: TPM exhibits stable anticonvulsant action against the tonic phase of generalized tonic-clonic seizures throughout development. In addition, it suppresses all phases of generalized seizures in 7-day-old rats. The anticonvulsant action of TPM lasted longer in 25-day-old than in 12-day-old rats. The two actions of TPM might be ascribed to two different mechanisms of action. [source] PRECLINICAL STUDY: Different effects of chronic phencyclidine on brain-derived neurotrophic factor in neonatal and adult rat brainsADDICTION BIOLOGY, Issue 2 2006Jun'ichi Semba ABSTRACT The N-methyl-D-aspartate (NMDA) receptor and brain-derived neurotrophic factor (BDNF) are both known to play major roles in the normal development of the brain. We have hypothesized that the chronic blockade of NMDA with phencyclidine (PCP) may have a different effect on BDNF synthesis at different stages of development. In an acute experiment, rat pups and adult rats were injected with PCP (2.5, 5 or 10 mg/kg) at postnatal day (PD) 15 or 49, respectively. In a chronic experiment, rat pups were injected daily from PD 5 to PD 14 with PCP (2.5, 5 or 10 mg/kg), while adult rats were injected daily with the same dose from PD 39 to PD 48. BDNF levels in the hippocampus, striatum and frontal cortex were determined by ELISA assay 24 hours after the last injection. Chronic PCP treatment of neonatal rats induced a dose-dependent decrease in BDNF in the hippocampus but not in the frontal cortex and striatum. Single injection of PCP to rat pups showed a slight reduction of BDNF in the hippocampus but only at higher doses. In contrast to neonatal brain, neither acute nor chronic injection of PCP influenced BDNF in adult brain. These findings suggest that chronic blockade of NMDA receptor in the early neonatal period has an inhibitory effect on BDNF synthesis in the hippocampus and may impair normal neurodevelopment in rat pups. [source] Extracellular signal-regulated kinase activation is required for consolidation and reconsolidation of memory at an early stage of ontogenesisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2009Solčne Languille Abstract The ability to form long-term memories exists very early during ontogeny; however, the properties of early memory processes, brain structures involved and underlying cellular mechanisms are poorly defined. Here, we examine the role of extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase/ERK signaling cascade, which is crucial for adult memory, in the consolidation and reconsolidation of an early memory using a conditioned taste aversion paradigm in 3-day-old rat pups. We show that intraperitoneal injection of SL327, the upstream mitogen-activated protein kinase kinase inhibitor, impairs both consolidation and reconsolidation of early memory, leaving short-term memory after acquisition and after reactivation intact. The amnesic effect of SL327 diminishes with increasing delays after acquisition and reactivation. Biochemical analyses revealed ERK hyperphosphorylation in the amygdala but not the hippocampus following acquisition, suggesting functional activation of the amygdala as early as post-natal day 3, although there was no clear evidence for amygdalar ERK activation after reactivation. These results indicate that, despite an immature brain, the basic properties of memory and at least some of the molecular mechanisms and brain structures implicated in aversion memory share a number of similarities with the adult and emerge very early during ontogeny. [source] 7-Hydroxylated epiandrosterone (7-OH-EPIA) reduces ischaemia-induced neuronal damage both in vivo and in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2003Ashley K. Pringle Abstract Recent evidence suggests that steroids such as oestradiol reduce ischaemia-induced neurodegeneration in both in vitro and in vivo models. A cytochrome P450 enzyme termed cyp7b that 7-hydroxylates many steroids is expressed at high levels in brain, although the role of 7-hydroxylated steroids is unknown. We have tested the hypothesis that the steroid-mediated neuroprotection is dependent on the formation of 7-hydroxy metabolites. Organotypic hippocampal slice cultures were prepared from Wistar rat pups and maintained in vitro for 14 days. Cultures were then exposed to 3 h hypoxia and neuronal damage assessed 24 h later using propidium iodide fluorescence as a marker of cell damage. Neurodegeneration occurred primarily in the CA1 pyramidal cell layer. The steroids oestradiol, dehydroepiandrosterone and epiandrosterone (EPIA) were devoid of neuroprotective efficacy when present at 100 nm pre-, during and post-hypoxia. The 7-hydroxy metabolites of EPIA, 7,-OH-EPIA and 7,-OH-EPIA significantly reduced neurotoxicity at 100 nm and 10 nm. 7,-OH-EPIA was also neuroprotective in two in vivo rat models of cerebral ischaemia: 0.1 mg/kg 7,-OH-EPIA significantly reduced hippocampal cell loss in a model of global forebrain ischaemia, whereas 0.03 mg/kg was neuroprotective in a model of focal ischaemia even when administration was delayed until 6 h after the onset of ischaemia. Taken together, these data demonstrate that 7-hydroxylation of steroids confers neuroprotective efficacy, and that 7,-OH-epiandrosterone represents a novel class of neuroprotective compounds with potential for use in acute neurodegenerative diseases. [source] Strain differences in the behavioural outcome of neonatal ventral hippocampal lesions are determined by the postnatal environment and not genetic factorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2001Graham K. Wood Abstract It has been demonstrated that not only do rats neonatally lesioned in the ventral hippocampus (VH) develop behavioural hypersensitivity to amphetamine postpubertally, but also that the expression of the sensitivity is strain specific. For example, excitotoxic VH lesions at postnatal day (PD) 7 lead to significant increases in amphetamine-induced locomotion in postpubertal Fischer rats, but not in Lewis rats. However, as it is likely that the effect of strain differences are due to a combination of genetics and environment, we examined the contributions of the environment of the pups in determining the behavioural outcome following neonatal VH lesions. Fisher and Lewis rat pups were cross-fostered at birth, and then at PD7 lesioned bilaterally in the VH with ibotenic acid. anova analysis of postpubertal amphetamine-induced locomotor data revealed a significant effect of the strain of the dams raising the pups but no effect of the strain of the pup. In addition, a post hoc analysis revealed that lesioned Fisher or Lewis rats raised by Fisher, but not those raised by Lewis, dams demonstrated amphetamine-induced hyperlocomotion relative to nonlesioned controls. Observations of the maternal behaviour of Fischer and Lewis dams revealed significant differences in the frequency of arched-back nursing between the two strains. Interestingly, a correlation of the frequency of arched back nursing vs novelty- or amphetamine-induced locomotion revealed that the lesioned rats were significantly more affected by increases in arched-back nursing compared to the controls. The results suggest that the genetic background of the pups does not significantly affect the behavioural outcome following neonatal VH lesions; however, the results do suggest an important role of early environmental variables on the behavioural outcome of neonatal VH lesions. [source] Alteration in regulation of inflammatory response to influenza a virus and endotoxin in suckling rat pups: a potential relationship to sudden infant death syndromeFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2004Jane Blood-Siegfried Abstract Data increasingly implicate a possible role of immune and inflammatory responses to infection in sudden infant death syndrome (SIDS). We have previously described a dual challenge model that results in pathology, organ damage, vascular collapse and unexplained death similar to that seen in SIDS. In this study, we examined changes in inflammatory cytokine mRNA in the lung and liver and regulation of pathways associated with nitric oxide production. Our data suggest that priming of the immune system by mild viral infection disturbs normal inflammatory response to endotoxin. This results in an increased nitric oxide synthase production, most likely the cause of liver pathology and clotting abnormalities. [source] PDGF stimulates the massive expansion of glial progenitors in the neonatal forebrainGLIA, Issue 16 2009M. C. Assanah Abstract Platelet-derived growth factor (PDGF) plays a major role in regulating migration, proliferation, and differentiation of glial progenitors during normal brain development and in the abnormal proliferation and dispersion that drives the formation of malignant gliomas. To further explore the relationship between PDGF's effects on normal glial progenitors and its role in the formation of gliomas, we infected progenitor cells in the subventricular zone (SVZ) of the lateral ventricle of neonatal rat pups with a retrovirus that expresses PDGF and green fluorescent protein (GFP). At 3 days post-injection (dpi), a proliferation of PDGFR,+ progenitors was seen in the SVZ and white matter around the injection site and by 10 dpi the animals had large diffusely infiltrating tumors that resembled glioblastomas. The tumors contained a massive proliferation of both infected and uninfected PDGFR,+ progenitors, suggesting that PDGF was driving tumor formation via both autocrine and paracrine signaling. Rats co-injected with two retroviruses (one that expresses PDGF-IRES-DSRED and one that expresses only GFP) formed tumors that contained a mixture of DSRED+ cells (PDGF producers) and GFP+ cells (recruited progenitors). Time-lapse microscopy of slice cultures confirmed that both DSRED+ and GFP+ cells were highly migratory and proliferative. Furthermore, adding exogenous PDGF to slice cultures generated from nontumor-bearing brains (injected with control GFP retrovirus only) stimulated the migration and proliferation of GFP+ progenitors. These findings reveal the inherent growth factor responsiveness and tumorigenic potential of PDGFR,+ progenitors and highlight the importance of paracrine signaling in stimulating glioma growth and infiltration. © 2009 Wiley-Liss, Inc. [source] Hippocampal mossy fiber sprouting and elevated trkB receptor expression following systemic administration of low dose domoic acid during neonatal developmentHIPPOCAMPUS, Issue 11 2007Paul B. Bernard Abstract We have previously reported that serial systemic injections of low-dose (subconvulsive) domoic acid (DOM) during early postnatal development produces changes in both behavior and hippocampal cytoarchitecture in aged rats (17 months) that are similar to those seen in existing animal models of temporal lobe epilepsy. Herein we report further hippocampal changes, consisting of mossy fiber sprouting and associated changes in the trkB receptor population in young adult (3 months) rats, and further, report that these changes show regional variation throughout the septo-temporal axis of the hippocampus. Groups of Sprague Dawley rat pups were injected daily from postnatal day 8,14 with either saline (n = 23) or 20 ,g/kg DOM (n = 25), tested for key indicators of neonatal neurobehavioral development, and then left undisturbed until ,90 days of age, at which time brain tissue was removed, hippocampi were dissected, fixed and processed using either Timm's stain to visualize hippocampal mossy fiber sprouting (MFS) or trkB immunohistochemistry to visualize full length trkB receptors. Multiple sections from dorsal, mid, and ventral hippocampus were analyzed separately and all measures were conducted using image analysis software. The results indicate significant increases in MFS in the inner molecular layer in treated animals with corresponding changes in trkB receptor density. Further we identified significant increases in trkB receptor density in the hilus of the dentate gyrus and area CA3 and report increased mossy fiber terminal density in the stratum lucidum in treated rats. The magnitude of these changes differed between sections from dorsal, mid, and ventral hippocampus. We conclude that low dose neonatal DOM produces cytoarchitectural changes indicative of abnormal development and/or synaptic plasticity that are progressive with age and show regional variation within the hippocampal formation. © 2007 Wiley-Liss, Inc. [source] Dexmedetomidine provides cortical neuroprotection: impact on anaesthetic-induced neuroapoptosis in the rat developing brainACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2010R. D. SANDERS Background: Recent evidence has demonstrated the anti-apoptotic of dexmedetomidine in different brain injury models. Herein, we investigated whether dexmedetomidine could directly protect against cortical injury in vitro and in vivo. Methods: Apoptosis was induced by staurosporine or wortmannin treatment in cortical neuronal cultures in vitro or by 6 h of isoflurane (0.75%) administration to post-natal day 7 rat pups in vivo. Dexmedetomidine was then applied in escalating doses to assess the neuroprotective potential of this agent. Cell survival was quantified using an MTT assay in vitro and in vivo apoptosis was assessed using cleaved caspase-3 immunohistochemistry. Cortical Western blots were conducted for the cellular survival proteins Bcl-2 and phosphorylated extracellular signal-regulated protein kinase (pERK)1 and 2. Results: In vitro dexmedetomidine dose-dependently prevented both staurosporine- and wortmannin-induced injury in cortical neuronal cultures, indicating that dexmedetomidine can prevent apoptosis when applied directly. In vivo isoflurane induced cortical neuroapoptosis compared with air (327±80 vs. 34±9 caspase-3-positive neurons; P<0.05). Dexmedetomidine inhibited isoflurane-induced caspase-3 expression (P<0.05), although the protection achieved did not completely attenuate the isoflurane injury (P<0.05 vs. air). Isoflurane treatment decreased Bcl-2 and pERK protein expression relative to air, an effect reversed by dexmedetomidine treatment. Conclusions: Dexmedetomidine prevents cortical apoptosis in vitro and in vivo. However, using higher doses of dexmedetomidine does not further increase protection against isoflurane injury in the cortex than previously observed. [source] Effects of postnatal ethanol exposure on neurotrophic factors and signal transduction pathways in rat brainJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2008Vittorio Fattori Abstract Exposure to ethanol during development induces severe brain damage, resulting in a number of CNS dysfunctions including microencephaly and mental retardation. Potential targets of ethanol-induced neurotoxicity include neurotrophic factors and their signal transduction pathways. In the present study, rat pups were given ethanol at the dose of 5 g kg,1 via gavage from postnatal day (PND) 5 to 8, and mRNA expression of nerve growth-factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophic factor-3 (NT-3) in the cerebral cortex was examined, with attention to signal transduction, on PND 8. The mRNA level of BDNF was decreased by ethanol while those of NGF or NT-3 were not changed. Brain weights were decreased and the levels of phospho-MAPK, phospho-p70S6K and phospho Akt were decreased while phosphor-PKC, and phospho-CREB remained unchanged. These results suggest that BDNF and its related signal pathways involving Akt, MAPK and p70S6K are potential targets of ethanol-induced developmental neurotoxicity. Copyright © 2007 John Wiley & Sons, Ltd. [source] Direct Inhibitory Effect of Glucocorticoids on Corticotrophin-Releasing Hormone Gene Expression in Neurones of the Paraventricular Nucleus in Rat Hypothalamic Organotypic CulturesJOURNAL OF NEUROENDOCRINOLOGY, Issue 9 2008B. Bali Corticotrophin-releasing hormone (CRH) in the parvocellular neurosecretory neurones of hypothalamic paraventricular nucleus governs neuroendocrine stress cascade and is the major target of the negative feedback effect of corticosteroids. To assess whether glucocorticoids exert their inhibitory effect on CRH expression directly on parvocellular neurones or indirectly through a complex neuronal circuit, we examined the effect of corticosterone (CORT) and dexamethasone (DEX) on CRH mRNA levels in slice explant cultures of the rat hypothalamus. Organotypic slice cultures were prepared from 6 days old rat pups and maintained in vitro for 14 days. CRH mRNA expression was measured by in situ hybridisation histochemistry. Under basal conditions, CRH mRNA expressing cells were exclusively revealed in the paraventricular region along the third ventricle. Inhibition of action potential spike activity by tetrodotoxin (TTX, 1 ,m) reduced CRH mRNA signal in the organotypic cultures. CORT (500 nm) or DEX (50 nm) treatment for 24 h significantly inhibited CRH expression in the parvocellular neurones and this effect of corticosteroids was not affected following blockade of voltage dependent sodium channels by TTX. Forskolin-stimulated CRH mRNA levels in the paraventricular nucleus were also inhibited by CORT or DEX in the presence and in the absence of TTX. These studies identify paraventricular CRH neurones as direct target of corticosteroid feedback. Type II corticosteroid receptor agonists act directly on paraventricular neurones to inhibit basal and forskolin-induced CRH mRNA expression in explant cultures of the rat hypothalamus. [source] Thyroid hormone stimulates ,-glutamyl transpeptidase in the developing rat cerebra and in astroglial culturesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2005Asmita Dasgupta Abstract Hypothyroidism in the developing rat brain is associated with enhanced oxidative stress, one of the earliest manifestations of which is a decline in the level of glutathione (GSH). To investigate the role of thyroid hormone (TH) on GSH homeostasis, the effect of TH on ,-glutamyl transpeptidase (,GT), the key enzyme involved in the catalysis of GSH, was studied. Hypothyroidism declined the specific activity of cerebral ,GT at all postnatal ages examined (postnatal day 1,20) with a maximum inhibition of 42% at postnatal day 10. Intraperitoneal injection of TH to 15-day-old rat pups increased the specific activity of ,GT by 25-30% within 4,6 hr. Treatment of primary cultures of astrocytes by TH also enhanced the specific activity of ,GT by 30,40% within 4,6 hr. The induction of ,GT by TH was blocked by actinomycin D or cycloheximide. ,GT is an ectoenzyme that is normally involved in the catabolism of GSH released by astrocytes. In the presence of the ,GT-inhibitor, acivicin, GSH released in the culture medium of astrocytes increased linearly for at least 6 hr and TH had no effect on this accumulation pattern. In the absence of acivicin, GSH content of the medium from TH-treated cells was significantly lower than that of untreated controls due to activation of ,GT by TH and a faster processing of GSH. Because the products of ,GT reaction are putative precursors for neuronal GSH, the activation of ,GT by TH may be conducive to GSH synthesis in neurons and their protection from oxidative stress. © 2005 Wiley-Liss, Inc. [source] Mild carbon monoxide exposure and auditory function in the developing ratJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2003Janet E. Stockard-Sullivan Abstract We have examined the influence of chronic mild exposure to carbon monoxide (CO) on cognitive (learning) and auditory function in the developing rat. We have demonstrated that the auditory pathway is compromised at exposures less than 50 ppm, whereas learning was not influenced at 100 ppm. Artificially reared rat pups were exposed to CO during the brain growth spurt and onset of myelination. Spatial learning was assessed using the Morris Water Maze and three tests of auditory function: (1) auditory brainstem conduction times; (2) the amplitude of the eighth nerve's action potential; and (3) otoacoustic emissions carried out on rat pups (age 22, 24 days). The pups were gastrostomy-reared on a rat milk substitute and chronically exposed to CO at discrete concentrations in the range of 12,100 ppm from 6 days of age to post-weaning at 21,23 days of age. We found no difference in auditory brainstem conduction times at all CO concentrations in comparison to non-exposed controls. There was a difference in otoacoustic emissions for test and controls at CO concentrations of 50 ppm but not at lower concentrations. There was a consistent attenuation of the amplitude of the eighth nerve's action potential, even at the lowest CO exposure examined. The attenuation of the amplitude of the action potential of the eighth nerve at 50 ppm carbon monoxide exposure did not completely recover by 73 days of age. We conclude that prolonged mild exposure to carbon monoxide during development causes measurable functional changes at the level of the eighth cranial nerve. © 2003 Wiley-Liss, Inc. [source] Isoflurane exerts a short-term but not a long-term preconditioning effect in neonatal rats exposed to a hypoxic-ischaemic neuronal injuryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2009N. SASAOKA Background: Isoflurane has been shown to induce tolerance against ischaemic injury in adult rodents. Although the delayed preconditioning effect of isoflurane has been demonstrated in neonatal rat pups, the acute preconditioning effects of isoflurane remained undetermined. The present study was therefore conducted to evaluate the acute preconditioning efficacy of isoflurane in neonatal rats subjected to a hypoxic-ischaemic (HI) injury. Methods: Post-natal day 7 pups were exposed to 1 or 2% isoflurane in oxygen for either 30, 60 or 90 min. Fifteen minutes after isoflurane exposure, the pups were subjected to an HI injury induced by left common carotid artery ligation and exposure to 8% oxygen for 2 h. Pups not exposed to isoflurane or not subjected to HI served as controls. Histopathologic injury to the cortex and hippocampus was evaluated 7 and 49 days after HI. Results: Isoflurane 2% exposure for 60 or 90 min before HI induced tolerance in the hippocampus and the number of normal neurons in the CA1 sector 7 days after HI was significantly greater than in non-preconditioned animals. This protective efficacy of isoflurane preconditioning was not observed 49 days after HI. Conclusions: Exposure of 2% isoflurane for at least 60 min is required to induce tolerance against HI injury in rat pups. However, this neuroprotective efficacy results in only transient neuroprotection. [source] Alterations in Circadian Rhythm Phase Shifting Ability in Rats Following Ethanol Exposure During the Third Trimester Brain Growth SpurtALCOHOLISM, Issue 5 2006Hiromi Sakata-Haga Background: Disruptions in sleep and feeding rhythms are among the consequences of prenatal alcohol exposure. Previously, we reported that ethanol exposure during the second trimester equivalent in rats produces long-lasting impairments in circadian system functioning. In the present study, we examined the effects of ethanol exposure during the third trimester equivalent brain growth spurt on the development of the circadian clock system. Methods: Sprague,Dawley male rat pups were exposed to 6.0 g/kg/d ethanol via an artificial rearing procedure on postnatal days (PD) 4 through 9 (EtOH). An artificially reared gastrostomized control group and a normally reared suckle control group were also included. At 10 to 12 weeks of age, wheel-running behavior was measured continuously under a 12-hour/12-hour light/dark (LD) cycle. Thereafter, subjects were exposed to a 6-hour phase delay of the LD cycle, and the ability to adjust to the new LD cycle was evaluated. Results: Before the phase delay, onset time of activity and acrophases of activity in all 3 groups were not significantly different from one another. After the 6-hour LD cycle delay, EtOH subjects were slower to adapt to the new cycle compared with both control groups, as measured by both activity onset and acrophase. Throughout the experiment, activity levels of EtOH subjects tended to be higher compared to both controls. Conclusions: These data demonstrate that ethanol exposure during the third trimester disrupts the ability to synchronize circadian rhythm to light cues. Disruptions in circadian regulation may cause abnormal behavioral rhythmicity, such as disrupted sleep and feeding patterns, as seen in individuals prenatally exposed to ethanol. [source] Antioxidant Pretreatment Does Not Ameliorate Alcohol-Induced Purkinje Cell Loss in the Developing Rat CerebellumALCOHOLISM, Issue 7 2005Jedidiah J. Grisel Background: Recent research has suggested that oxidative stress is a potential mechanism for alcohol-induced injury and that supplementation with antioxidants can ameliorate alcohol-induced damage. In this study, two known antioxidants, melatonin and U83836E, were assessed for their effectiveness in blocking the expected alcohol-induced cerebellar Purkinje cell loss in neonatal rat pups. Methods: Sprague-Dawley rat pups were artificially reared from postnatal days (PDs) 4,9 and were exposed to either alcohol or antioxidants (melatonin or U83836E) individually or in combination. A normal control group (raised by rat dams) was included in this study. On PD 9, the brain from each pup was removed and weighed, and the cerebellar vermis was processed for stereological cell counting. Results: Alcohol exposure during the brain growth spurt produced microencephaly, in addition to significant decreases in the number and density of Purkinje cells in lobule I and the volume of lobule I. The antioxidants did not reduce any of the adverse effects observed from alcohol exposure, and they did not decrease the Purkinje cell number when administered alone. Furthermore, antioxidants did not change the only blood alcohol concentration measured on PD 6. Conclusions: The results confirmed alcohol-induced microencephaly and cerebellar Purkinje cell loss from neonatal alcohol exposure, and they showed that neither antioxidant could attenuate these adverse effects on the developing brain. The inability of antioxidants to reduce Purkinje cell loss from neonatal alcohol exposure suggests the existence of alternative mechanisms for developmental alcohol-induced Purkinje cell loss. [source] | |||||||||||||