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Specific Brain Regions (specific + brain_regions)
Selected AbstractsPalatable High-Energy Diet Decreases the Expression of Cannabinoid Type 1 Receptor Messenger RNA in Specific Brain Regions in the RatJOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2009E. Timofeeva In laboratory rodents, a palatable high-energy diet (PHED) is usually consumed in a higher quantity than a standard laboratory diet, leading to the development of an obese phenotype. The central effects of PHED are not fully understood. Nonetheless, the long-term consumption of PHED can decrease cannabinoid type 1 receptor (CB1R) protein density in particular brain regions. However, little is known about the diet-dependent regulation of the brain expression of CB1R mRNA. The present study aimed to investigate the effects of the long-term consumption of PHED and short-term (12 h) food deprivation on the brain expression of CB1R mRNA. For 13 weeks, rats were fed a standard laboratory chow or PHED presented as a free choice of chow, shortcake biscuits and pork spread. In total, the food intake of PHED rats was higher than that of chow-fed animals. Expectedly, PHED rats demonstrated higher body weight than chow-fed animals. The difference in body weight between PHED- and chow-fed rats was as result of the fat but not the lean mass. PHED-fed rats had significantly higher plasma levels of leptin and insulin and significantly higher levels of expression of suppressor of cytokine signalling 3 (SOCS-3) in the arcuate hypothalamic nucleus. The long-term consumption of PHED significantly decreased the levels of CB1R mRNA expression in the cingulate (Cg) cortex, ventromedial hypothalamic nucleus and the descending/autonomic divisions of the parvocellular hypothalamic nucleus (PVH), the ventrolateral parvocellular PVH and, to a lesser extent, the dorsomedial parvocellular PVH. Acute food deprivation decreased the levels of CB1R transcript in the Cg and ventrolateral parvocellular PVH. Altogether, the present results demonstrate that long-term PHED leads to an increase in the hypothalamic expression of SOCS-3 mRNA and a decrease in expression of CB1R mRNA in the Cg cortex and specific hypothalamic regions. [source] cadherin-6 Message expression in the nervous system of developing zebrafishDEVELOPMENTAL DYNAMICS, Issue 1 2006Qin Liu Abstract Cadherins are cell surface adhesion molecules that play important roles in development of a variety of tissues including the nervous system. In this study, we analyzed expression pattern of cadherin-6, a member of the type II cadherin subfamily, in the embryonic zebrafish nervous system using in situ hybridization methods. cadherin-6 message is first expressed by the neural keel, then by restricted regions in the brain and spinal cord. cadherin-6 expression in the brain transiently delineates specific brain regions. In the peripheral nervous system, cadherin-6 message is expressed by the neurogenic placodes and the dorsal root ganglia. As development proceeds, cadherin-6 expression domain and/or expression levels increased in the embryonic nervous system. Our results show that cadherin-6 expression in the zebrafish developing nervous system is both spatially and temporally regulated, implicating a role for cadherin-6 in the formation of these nervous structures. Developmental Dynamics 235:272,278, 2006. © 2005 Wiley-Liss, Inc. [source] Altered Tryptophan Metabolism in the Brain of Cystatin B -Deficient Mice: A Model System for Progressive Myoclonus EpilepsyEPILEPSIA, Issue 10 2006Annika Vaarmann Summary:,Purpose: Progressive myoclonus epilepsy of the Unverricht,Lundborg type (EPM1) is a rare neurologic disorder, associated with mutations in the Cystatin B (Cstb) gene. Mice lacking Cstb, a cysteine protease inhibitor of the cathepsine family of proteases, provide a mammalian model for EPM1 by displaying similarly progressive ataxia, myoclonic seizures, and neurodegeneration. However, the linkage of Cstb deficit on the molecular level to pathologic features like myoclonic jerks or tonic,clonic seizures has remained unclear. We examined the tryptophan (TRP) metabolism, along the serotonin (5HT) and kynurenine (KYN) pathway in the brain of Cstb -deficient mice, in relation to their possible involvement in the seizure phenotype. Methods: TRP and its metabolites, along the 5HT and KYN pathways, were assayed in brain tissue by high-pressure liquid chromatography (HPLC) with electrochemical detection. The inverted wire grid and mild handling tests were used for evaluation of ataxia and myoclonic activity. Results: The Cstb -deficient mice had constitutively increased TRP, 5HT, and 5-hydroxyindole acetic acid (5HIAA) levels in the cerebral cortex and cerebellum and increased levels of KYN in the cerebellum. These neurochemical changes were accompanied with ataxia and an apparent myoclonic phenotype among the Cstb -deficient mice. Conclusions: Our findings suggest that secondary processes (i.e., overstimulation of serotoninergic transmission) on the cellular level, initiated by Cstb deficiency in specific brain regions, may be responsible for the myoclonic/seizure phenotype in EPM1. [source] Long-range connectivity of mouse primary somatosensory barrel cortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2010Rachel Aronoff Abstract The primary somatosensory barrel cortex processes tactile vibrissae information, allowing rodents to actively perceive spatial and textural features of their immediate surroundings. Each whisker on the snout is individually represented in the neocortex by an anatomically identifiable ,barrel' specified by the segregated termination zones of thalamocortical axons of the ventroposterior medial nucleus, which provide the primary sensory input to the neocortex. The sensory information is subsequently processed within local synaptically connected neocortical microcircuits, which have begun to be investigated in quantitative detail. In addition to these local synaptic microcircuits, the excitatory pyramidal neurons of the barrel cortex send and receive long-range glutamatergic axonal projections to and from a wide variety of specific brain regions. Much less is known about these long-range connections and their contribution to sensory processing. Here, we review current knowledge of the long-range axonal input and output of the mouse primary somatosensory barrel cortex. Prominent reciprocal projections are found between primary somatosensory cortex and secondary somatosensory cortex, motor cortex, perirhinal cortex and thalamus. Primary somatosensory barrel cortex also projects strongly to striatum, thalamic reticular nucleus, zona incerta, anterior pretectal nucleus, superior colliculus, pons, red nucleus and spinal trigeminal brain stem nuclei. These long-range connections of the barrel cortex with other specific cortical and subcortical brain regions are likely to play a crucial role in sensorimotor integration, sensory perception and associative learning. [source] Sex differences in anxiety, sensorimotor gating and expression of the ,4 subunit of the GABAA receptor in the amygdala after progesterone withdrawalEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003M. Gulinello Abstract In a progesterone withdrawal (PWD) model of premenstrual anxiety, we have previously demonstrated that increased hippocampal expression of the ,4 subunit of the GABAA receptor (GABAA -R) is closely associated with higher anxiety levels in the elevated plus maze. However, several studies indicate that sex differences in regulation of the GABAA -R in specific brain regions may be an important factor in the observed gender differences in mood disorders. Thus, we investigated possible sex differences in GABAA -R subunit expression and anxiety during PWD. To this end, we utilized the acoustic startle response (ASR) to assess anxiety levels in male and female rats undergoing PWD as the ASR is also applicable to the assessment of human anxiety responses. We also investigated GABAA -R ,4 subunit expression in the amygdala, as the amygdala directly regulates the primary startle circuit. Female rats exhibited a greater ASR during PWD than controls, indicating higher levels of anxiety and arousal. In contrast, male rats undergoing PWD did not demonstrate an increased ASR. The sex differences in the ASR were paralleled by sex differences in the expression of the GABAA -R ,4 subunit in the amygdala such that ,4 subunit expression was up-regulated in females during PWD whereas ,4 levels in males undergoing PWD were not altered relative to controls. These findings might have implications regarding gender differences in human mood disorders and the aetiology of premenstrual anxiety. [source] Involvement of the inferior frontal junction in cognitive control: Meta-analyses of switching and Stroop studiesHUMAN BRAIN MAPPING, Issue 1 2005Jan Derrfuss Abstract There is growing evidence that a specific region in the posterior frontolateral cortex is involved intimately in cognitive control processes. This region, located in the vicinity of the junction of the inferior frontal sulcus and the inferior precentral sulcus, was termed the inferior frontal junction (IFJ). The IFJ was shown to be involved in the updating of task representations and to be activated commonly in a within-subject investigation of a task-switching paradigm, the Stroop task, and a verbal n-back task. Here, we investigate the involvement of the IFJ in cognitive control by employing a meta-analytic approach. Two quantitative meta-analyses of functional magnetic resonance imaging (fMRI) studies were conducted. One meta-analysis included frontal activations from task-switching, set-shifting, and stimulus,response (S,R) reversal studies, the other included frontal activations from color,word Stroop studies. Results showed highly significant clustering of activations in the IFJ in both analyses. These results provide strong evidence for the consistent involvement of the IFJ in both switching and Stroop paradigms. Furthermore, they support our concept of areal specialization in the frontolateral cortex, which posits that it is not only the middorsolateral part that plays an important role in cognitive control, but also the IFJ. Finally, our results demonstrate how quantitative meta-analyses can be used to test hypotheses about the involvement of specific brain regions in cognitive control. Hum Brain Mapp 25:22,34, 2005. © 2005 Wiley-Liss, Inc. [source] Regional cerebral blood flow responses to hyperventilation during sevoflurane anaesthesia studied with PETACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2010L. SCHLÜNZEN Background: Arterial carbon dioxide tension (PaCO2) is an important factor controlling cerebral blood flow (CBF) in neurosurgical patients. It is still unclear whether the hypocapnia-induced decrease in CBF is a general effect on the brain or rather linked to specific brain regions. We evaluated the effects of hyperventilation on regional cerebral blood flow (rCBF) in healthy volunteers during sevoflurane anaesthesia measured with positron emission tomography (PET). Methods: Eight human volunteers were anaesthetized with sevoflurane 1 MAC, while exposed to hyperventilation. During 1 MAC sevoflurane at normocapnia and 1 MAC sevoflurane at hypocapnia, one H215O scan was performed. Statistical parametric maps and conventional regions of interest analysis were used for estimating rCBF differences. Results: Cardiovascular parameters were maintained constant over time. During hyperventilation, the mean PaCO2 was decreased from 5.5 ± 0.7 to 3.8 ± 0.9 kPa. Total CBF decreased during the hypocapnic state by 44%. PET revealed wide variations in CBF between regions. The greatest values of vascular responses during hypocapnia were observed in the thalamus, medial occipitotemporal gyrus, cerebellum, precuneus, putamen and insula regions. The lowest values were observed in the superior parietal lobe, middle and inferior frontal gyrus, middle and inferior temporal gyrus and precentral gyrus. No increases in rCBF were observed. Conclusions: This study reports highly localized and specific changes in rCBF during hyperventilation in sevoflurane anaesthesia, with the most pronounced decreases in the sub cortical grey matter. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve during hypocapnia. [source] Controlled and localized genetic manipulation in the brainJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2006Rachel Aronoff Abstract Brain structure and function are determined in part through experience and in part through our inherited genes. A powerful approach for unravelling the balance between activity-dependent neuronal plasticity and genetic programs is to directly manipulate the genome. Such molecular genetic studies have been greatly aided by the remarkable progress of large-scale genome sequencing efforts. Sophisticated mouse genetic manipulations allow targeted point-mutations, deletions and additions to the mouse genome. These can be regulated through inducible promoters expressing in genetically specified neuronal cell types. However, despite significant progress it remains difficult to target specific brain regions through transgenesis alone. Recent work suggests that transduction vectors, like lentiviruses and adeno-associated viruses, may provide suitable additional tools for localized and controlled genetic manipulation. Furthermore, studies with such vectors may aid the development of human genetic therapies for brain diseases. [source] A novel effect of rivastigmine on pre-synaptic proteins and neuronal viability in a neurodegeneration model of fetal rat primary cortical cultures and its implication in Alzheimer's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 4 2010Jason A. Bailey J. Neurochem. (2010) 112, 843,853. Abstract Alzheimer's disease (AD) is characterized by deposition of amyloid-, peptide plaque, disrupted amyloid-,-precursor protein (APP) metabolism, hyperphosphorylation of Tau leading to neurofibrillary tangles and associated neurotoxicity. Moreover, there is synaptic loss in AD, which occurs early and may precede frank amyloidosis. The central cholinergic system is especially vulnerable to the toxic events associated with AD, and reduced acetylcholine levels in specific brain regions is thought to be central to memory deficits in AD. First-generation cholinesterase inhibitors have provided only symptomatic relief to patients with AD by prolonging the action of remaining acetylcholine with little or no change in the course of the disease. Some second-generation cholinesterase inhibitors are multifunctional drugs that may provide more than purely palliative results. To evaluate the effects of the dual acetylcholinesterase and butyrylcholinesterase inhibitor rivastigmine on key aspects of AD, embryonic day 16 rat primary cortical cultures were treated with rivastigmine under media conditions observed to induce time-dependent neurodegeneration. Samples were subjected to western blotting and immunocytochemistry techniques to determine what influence this drug may have on synaptic proteins and neuronal morphology. There was a strong increase in relative cell viability associated with rivastigmine treatment. Significant dose-dependent increases were observed in the levels of synaptic markers synaptosomal-associated protein of 25 kDa (SNAP-25) and synaptophysin, as well as the neuron-specific form of enolase. Together with an observed enhancement of neuronal morphology, our results suggest a rivastigmine-mediated novel neuroprotective and/or neurorestorative effects involving the synapse. Our observations may explain the potential for rivastigmine to alter the course of AD, and warrant further investigations into using butyrylcholinesterase inhibition as a therapeutic strategy for AD, especially with regard to restoration of synaptic function. [source] Regional brain serotonin synthesis is increased in the olfactory bulbectomy rat model of depression: an autoradiographic studyJOURNAL OF NEUROCHEMISTRY, Issue 2 2003Arata Watanabe Abstract Serotonin synthesis rates were evaluated using ,-[14C]methyl- l -tryptophan (,-MTrp) autoradiographic methods in olfactory bulbectomized (OBX) rats. They were significantly (p < 0.05) increased in the frontal (50%) and parietal (40%) cortices, superior olive (over 30%), and the substantia nigra (30%) in the OBX rats as compared to the sham operated animals. There were also increases in 5-hydroxytryptamine (5-HT) synthesis in some limbic areas: the cingulate (32%), the medial forebrain bundle (58%), the hippocampus (13,25%) and the thalamus (22,40%). The largest increase in 5-HT synthesis after OBX was observed in the sensory-motor cortex (67%). 5-HT synthesis rates were significantly decreased in the dorsal and medial raphe nuclei, but there was no significant change the ventral tegmental area and the locus coeruleus following OBX. These results indicate that olfactory bulbectomy causes an imbalance in 5-HT synthesis in some projection areas by disproportionally increasing 5-HT synthesis rates in specific brain regions and making more 5-HT available for neurotransmission. This imbalance in 5-HT synthesis and the subsequent elevation of tissue 5-HT may be responsible for the creation of non-physiological circuitry which may, in part, be reflected in the symptoms resembling human depression. [source] Structure of the Mouse Glutamate Decarboxylase 65 Gene and Its PromoterJOURNAL OF NEUROCHEMISTRY, Issue 4 2000Preferential Expression of Its Promoter in the GABAergic Neurons of Transgenic Mice Abstract: GABA is synthesized by glutamate decarboxylase (GAD), which has two forms, GAD65 and GAD67. To elucidate the molecular mechanisms of mouse GAD65 (mGAD65) gene expression, we isolated and characterized the mGAD65 gene. The mGAD65 gene was found to be divided into 16 exons and spread over 75 kb. The sequence of the first exon and the 5,-flanking region indicated the presence of potential neuron-specific cis -regulatory elements. We used transgenic mice to examine the expression pattern conferred by a 9.2-kb promoter-proximal DNA fragment of the mGAD65 gene fused to the bacterial lacZ reporter gene. Transgenic mice showed high ,-galactosidase activity specifically in brain and testis. They also showed characteristic patterns of transgene expression in olfactory bulb, cerebellar cortex, and spinal cord, a similar expression pattern to that of endogenous mGAD65. However, no transgene expression was observed in the ventral thalamus or hypothalamus, in which high mGAD65 gene expression levels have been observed. These results suggest that the 9.2-kb DNA fragment of the mGAD65 gene is associated with its tissue-specific expression and its targeted expression in GABAergic neurons of specific brain regions but that additional regulatory elements are necessary to obtain fully correct expression. [source] Sex Differences in Oestrogen-Induced p44/42 MAPK Phosphorylation in the Mouse Brain In VivoJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2006K. Barabás In addition to the classical direct genomic mechanisms of action, oestrogen also exerts poorly understood, nonclassical effects on the signalling system in neurones. In the present study, we investigated whether sex differences exist in gonadectomy- and oestrogen-induced effects on p44/42 mitogen-activated protein kinase (MAPK) phosphorylation in specific brain regions of mice. We demonstrate that MAPK immunoreactivity was not altered by gonadectomy or oestrogen treatment in either sex. However, we show that the level of phosphorylated MAPK (pMAPK) within the anteroventral periventricular nucleus (AVPV) was consistently higher in males than females irrespective of gonadal steroid hormone status. In addition, gonadectomy was found to decrease pMAPK immunoreactivity within the piriform cortex of males. Oestrogen increased pMAPK immunoreactivity in the medial preoptic area and AVPV of females, but failed to have the same effect in male mice. Overall, these results demonstrate a marked sex difference in oestrogen-induced alteration of MAPK phosphorylation in the brain in vivo. [source] Dietary lithium induces regional increases of mRNA encoding cysteine string protein in rat brainJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2003Mara L. Cordeiro Abstract Lithium salts are used to treat manic-depressive disorders; however, the mechanism by which lithium produces its therapeutic benefit remains obscure. The action of lithium may involve alterations of proteins important for regulating synaptic function. In this context, we observed recently that lithium at therapeutically relevant concentrations enhanced expression of cysteine string protein (csp) at the level of both mRNA and protein, in cell culture and in rat brain. Several lines of evidence have shown that csps are vital components of the regulated secretory pathway. We were interested whether lithium modulates expression of csp in specific brain regions. To study this issue, we analyzed the effects of chronic lithium administration (21 days) on csp mRNA levels in rat brain using in situ hybridization. Densitometric analysis revealed that lithium upregulated csp mRNA in several brain areas that are important for mood and behavior. This effect may be germane to understanding the beneficial action of lithium in mood disorders. © 2003 Wiley-Liss, Inc. [source] Functional Brain Mapping of Extraversion and Neuroticism: Learning From Individual Differences in Emotion ProcessingJOURNAL OF PERSONALITY, Issue 6 2004Turhan Canli Studies using functional magnetic resonance imaging have shown that individual differences in participants' E and N scores are correlated with individual differences in brain activation in specific brain regions that are engaged during cognitive-affective tasks. Imaging studies using genotyped participants have begun to address the molecular mechanisms that may underlie these individual differences. The multidisciplinary integration of brain imaging and molecular genetic methods offers an exciting and novel approach for investigators who seek to uncover the biological mechanisms by which personality and health are interrelated. [source] Ethanol-Induced Increase of Agouti-Related Protein (AgRP) Immunoreactivity in the Arcuate Nucleus of the Hypothalamus of C57BL/6J, but not 129/SvJ, Inbred MiceALCOHOLISM, Issue 4 2010Inmaculada Cubero Background:, The melanocortin (MC) system is composed of peptides that are cleaved from the polypeptide precursor, pro-opiomelanocortin (POMC). Previous research has shown that MC receptor (MCR) agonists reduce, and MCR antagonists increase, ethanol consumption in rats and mice. Consistently, genetic deletion of the endogenous MCR antagonist, agouti-related protein (AgRP), causes reductions of ethanol-reinforced lever pressing and binge-like ethanol drinking in C57BL/6J mice. Ethanol also has direct effects on the central MC system, as chronic exposure to an ethanol-containing diet causes significant reductions of ,-melanocyte stimulating hormone (,-MSH) immunoreactivity in specific brain regions of Sprague-Dawley rats. Together, these observations suggest that the central MC system modulates neurobiological responses to ethanol. To further characterize the role of the MC system in responses to ethanol, here we compared AgRP and ,-MSH immunoreactivity in response to an acute injection of saline or ethanol between high ethanol drinking C57BL/6J mice and moderate ethanol drinking 129/SvJ mice. Methods:, Mice received an intraperitoneal (i.p.) injection of ethanol (1.5 g/kg or 3.5 g/kg; mixed in 0.9% saline) or an equivolume of 0.9% saline. Two hours after injection, animals were sacrificed and their brains were processed for AgRP and ,-MSH immunoreactivity. Results:, Results indicated that acute ethanol administration triggered a dose-dependent increase in AgRP immunoreactivity in the arcuate (ARC) of C57BL/6J mice, an effect that was not evident in the 129/SvJ strain. Although acute administration of ethanol did not influence ,-MSH immunoreactivity, C57BL/6J mice had significantly greater overall ,-MSH immunoreactivity in the ARC, dorsomedial, and lateral regions of the hypothalamus relative to the 129/SvJ strain. In contrast, C57BL/6J mice displayed significantly lower ,-MSH immunoreactivity in the medial amygdala. Conclusions:, The results show that acute ethanol exposure has direct effects on endogenous AgRP activity in ethanol preferring C57BL/6J mice. It is suggested that ethanol-induced increases in AgRP may be part of a positive feedback system that stimulates excessive binge-like ethanol drinking in C57BL/6J mice. Inherent differences in ,-MSH immunoreactivity may contribute to differences in neurobiological responses to ethanol that are characteristically observed between the C57BL/6J and 129/SvJ inbred strains of mice. [source] Ethanol-Sensitive Brain Regions in Rat and Mouse: A Cartographic Review, Using Immediate Early Gene ExpressionALCOHOLISM, Issue 6 2009Catherine Vilpoux Background:, Ethanol addiction has been conceptualized as a progression from occasional, impulsive use to compulsive behavior. Ethanol-dependence is a chronic pathology with repeated cycles of withdrawal, craving, and relapse. Specific molecular and cellular mechanisms underlie these transition stages. Methods:, This review aimed at elucidating whether there are also adaptations in the pattern of brain regions responding to ethanol. This paper reviews the evidence in rodents for activation of specific brain regions, assessed by induction of IEG expression, following acute and chronic ethanol exposure. Results:, The review sheds light on the specific patterns of response in regions of the brain to different types of ethanol exposure and shows that activation of specific brain regions may occur in particular phases of the development of ethanol addiction. Some brain regions respond consistently following acute or chronic treatments or withdrawal: the prefrontal cortex; nucleus accumbens; lateral septum; hippocampus; perioculomotor urocortin-containing cells population (pIIIu), also known as Edinger-Westphal nucleus; central nucleus of the amygdale; and the paraventricular nucleus of hypothalamus. The two last brain areas are particularly activated by relapse-inducing stressors. It is of interest that the amygdala, hippocampus, and prefrontal cortex, which belong to the reward system, are activated by cue-induced relapse to ethanol self-administration in rodents and humans, while activation of these regions is reversed with anticraving compounds. Following chronic exposure, IEG induction desensitizes while withdrawal reactivates these regions. Discussion:, Some responding regions are implicated in reward related processes (VTA, extended amygdala, hypothalamus, hippocampus, prelimbic cortex, ventral part of lateral septum) and some others in aversive-related processes (area postrema, nucleus of solitary tract). Conclusion:, A better understanding of the neural circuits affected by ethanol and their adaptations during the development of ethanol addiction will provide new opportunities for developing appropriate therapies. [source] Magnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 8ALCOHOLISM, Issue 6 2009Scott E. Parnell Background:, Magnetic resonance microscopy (MRM), magnetic resonance imaging (MRI) at microscopic levels, provides unprecedented opportunities to aid in defining the full spectrum of ethanol's insult to the developing brain. This is the first in a series of reports that, collectively, will provide an MRM-based atlas of developmental stage-dependent structural brain abnormalities in a Fetal Alcohol Spectrum Disorders (FASD) mouse model. The ethanol exposure time and developmental stage examined for this report is gestational day (GD) 8 in mice, when the embryos are at early neurulation stages; stages present in humans early in the fourth week postfertilization. Methods:, For this study, pregnant C57Bl/6J mice were administered an ethanol dosage of 2.8 g/kg intraperitoneally at 8 days, 0 hour and again at 8 days, 4 hours postfertilization. On GD 17, fetuses that were selected for MRM analyses were immersion fixed in a Bouin's/Prohance® solution. Control fetuses from vehicle-treated dams were stage-matched to those that were ethanol-exposed. The fetal mice were scanned ex vivo at 7.0 T and 512 × 512 × 1024 image arrays were acquired using 3-D spin warp encoding. The resulting 29 ,m (isotropic) resolution images were processed using ITK-SNAP, a 3-D segmentation/visualization tool. Linear and volume measurements were determined for selected brain, head, and body regions of each specimen. Comparisons were made between control and treated fetuses, with an emphasis on determining (dis)proportionate changes in specific brain regions. Results:, As compared with controls, the crown-rump lengths of stage-matched ethanol-exposed GD 17 fetuses were significantly reduced, as were brain and whole body volumes. Volume reductions were notable in every brain region examined, with the exception of the pituitary and septal region, and were accompanied by increased ventricular volumes. Disproportionate regional brain volume reductions were most marked on the right side and were significant for the olfactory bulb, hippocampus, and cerebellum; the latter being the most severely affected. Additionally, the septal region and the pituitary were disproportionately large. Linear measures were consistent with those of volume. Other dysmorphologic features noted in the MR scans were choanal stenosis and optic nerve coloboma. Conclusions:, This study demonstrates that exposure to ethanol occurring in mice at stages corresponding to the human fourth week postfertilization results in structural brain abnormalities that are readily identifiable at fetal stages of development. In addition to illustrating the utility of MR microscopy for analysis of an FASD mouse model, this work provides new information that confirms and extends human clinical observations. It also provides a framework for comparison of structural brain abnormalities resulting from ethanol exposure at other developmental stages and dosages. [source] Upregulation of ,-Catenin Levels in Superior Frontal Cortex of Chronic AlcoholicsALCOHOLISM, Issue 6 2008Ali M. Al-Housseini Background:, Chronic and excessive alcohol misuse results in neuroadaptive changes in the brain. The complex nature of behavioral, psychological, emotional, and neuropathological characteristics associated with alcoholism is likely a reflection of the network of proteins that are affected by alcohol-induced gene expression patterns in specific brain regions. At the molecular level, however, knowledge remains limited regarding alterations in protein expression levels affected by chronic alcohol abuse. Thus, novel techniques that allow a comprehensive assessment of this complexity will enable the simultaneous assessment of changes across a group of proteins in the relevant neural circuitry. Methods:, A proteomics analysis was performed using antibody microarrays to determine differential protein levels in superior frontal cortices between chronic alcoholics and age- and gender-matched control subjects. Seventeen proteins related to the catenin signaling pathway were analyzed, including ,-, ,-, and ,-catenins, their upstream activators cadherin-3 (type I cadherin) and cadherin-5 (type II cadherin), and 5 cytoplasmic regulators c-Src, CK1,, GSK-3,, PP2A-C,, and APC, as well as the nuclear complex partner of ,-catenin CBP and 2 downstream genes Myc and cyclin D1. ILK, G,1, G,1, and G,2, which are activity regulators of GSK-3,, were also analyzed. Results:, Both ,- and ,-catenin showed significantly increased levels, while ,-catenin did not change significantly, in chronic alcoholics. In addition, the level of the ,-catenin downstream gene product Myc was significantly increased. Average levels of the catenin regulators c-Src, CK1,, and APC were also increased in chronic alcoholics, but the changes were not statistically significant. Conclusion:, Chronic and excessive alcohol consumption leads to an upregulation of ,- and ,-catenin levels, which in turn increase downstream gene expressions such as Myc that is controlled by ,-catenin signaling. This study showed that the ,-catenin signal transduction pathway was upregulated by chronic alcohol abuse, and prompts further investigation of mechanisms underlying the upregulation of ,- and ,-catenins in alcoholism, which may have considerable pathogenic and therapeutic relevance. [source] Alcohol-Induced Neurodegeneration: When, Where and Why?ALCOHOLISM, Issue 2 2004Fulton T. Crews Abstract: This manuscript reviews the proceedings of a symposium organized by Drs. Antonio Noronha and Fulton Crews presented at the 2003 Research Society on Alcoholism meeting. The purpose of the symposium was to examine recent findings on when alcohol induced brain damage occurs, e.g., during intoxication and/or during alcohol withdrawal. Further studies investigate specific brain regions (where) and the mechanisms (why) of alcoholic neurodegeneration. The presentations were (1) Characterization of Synaptic Loss in Cerebella of Mature and Senescent Rats after Lengthy Chronic Ethanol Consumption, (2) Ethanol Withdrawal Both Causes Neurotoxicity and Inhibits Neuronal Recovery Processes in Rat Organotypic Hippocampal Cultures, (3) Binge Drinking-Induced Brain Damage: Genetic and Age Related Effects, (4) Binge Ethanol-Induced Brain Damage: Involvement of Edema, Arachidonic Acid and Tissue Necrosis Factor , (TNF,), and (5) Cyclic AMP Cascade, Stem Cells and Ethanol. Taken together these studies suggest that alcoholic neurodegeneration occurs through multiple mechanisms and in multiple brain regions both during intoxication and withdrawal. [source] Expression of c-Fos in Alko Alcohol Rats Responding for Ethanol in an Operant ParadigmALCOHOLISM, Issue 5 2001Adam Z. Weitemier Background: Identification of the brain regions involved in ethanol administration is important for understanding the neurobiology of ethanol addiction. Animal studies with different brain mapping techniques found that voluntary ethanol self-administration leads to changes in activity of specific brain regions in patterns that only partially overlap with patterns of brain regions affected by involuntary (i.e., experimenter-administered) ethanol administration. As an extension of studies mapping changes in neural activity after voluntary ethanol drinking, this study analyzed expression of the inducible transcription factor c-Fos after ethanol consumption in an operant procedure. Methods: AA (Alko alcohol) rats were trained to operantly respond for water, 0.2% saccharin, 0.2% saccharin/10% (w/v) ethanol, or 10% ethanol in a 30-min limited-access procedure. Animals were allowed to self-administer solutions for at least 40 ethanol response sessions and were killed 1.5 hr after beginning of the last session. Forty-seven brain regions were immunohistochemically analyzed for c-Fos expression. Results: In this paradigm, ethanol dose-dependently increased c-Fos expression in the Edinger-Westphal nucleus (EW) and decreased expression in the dorsal tenia tecta compared with no-ethanol controls. No effects of saccharin on c-Fos expression were found. Conclusions: Our results extend previous findings of preferential sensitivity of EW to alcohol in voluntary self-administration procedures to operant responding for ethanol and warrant further investigation of ethanol's effects on the EW. The finding that ethanol attenuated c-Fos expression in the tenia tecta is novel. Taken together, these findings confirm that voluntary ethanol self-administration leads to changes in activity of a limited number of brain regions with previously unexamined roles in ethanol sensitivity and addiction. [source] IR-SE and IR-MEMRI allow in vivo visualization of oscine neuroarchitecture including the main forebrain regions of the song control systemNMR IN BIOMEDICINE, Issue 1 2006Ilse Tindemans Abstract Songbirds share with humans the capacity to produce learned vocalizations (song). Recently, two major regions within the songbird's neural substrate for song learning and production; nucleus robustus arcopallii (RA) and area X (X) are visualized in vivo using Manganese Enhanced MRI (MEMRI). The aim of this study is to extend this to all main interconnected forebrain Song Control Nuclei. The ipsilateral feedback circuits allow Mn2+ to reach all main Song Control Nuclei after stereotaxic injection of very small doses of MnCl2 (10,nl of 10,mM) into HVC of one and MAN (nucleus magnocellularis nidopallii anterioris) of the other hemisphere. Application of a high resolution (80,µ) Spin Echo Inversion Recovery sequence instead of conventional T1-weighted Spin Echo images improves the image contrast dramatically such that some Song Control Nuclei, ventricles, several laminae, fibre tracts and other specific brain regions can be discerned. The combination of this contrast-rich IR-SE sequence with the transsynaptic transport property of Manganese (Inversion Recovery based MEMRI (IR-MEMRI)) enables the visualization of all main interconnected components of the Song Control System in telencephalon and thalamus. Copyright © 2006 John Wiley & Sons, Ltd. [source] A comparative analysis of constitutive and cell-specific promoters in the adult mouse hippocampus using lentivirus vector-mediated gene transferTHE JOURNAL OF GENE MEDICINE, Issue 11 2008Hitoshi Kuroda Abstract Background Viral vectors provide powerful tools for transgene delivery to the mammalian brain to assess the effects of therapeutic proteins, antisense RNAs or small interfering RNAs. A key advantage of such approaches is that specific brain regions implicated in a particular disease can be independently targeted. Methods To optimize transgene expression in sub-regions of the mouse hippocampus and with a view towards devising gene therapy strategies for Alzheimer's disease, we designed lentivirus-based reporter vectors bearing various promoters, including constitutive and cell-specific promoters. Furthermore, we devised methods allowing a side-by-side comparison of transgene expression levels in neural cells both in vitro and in vivo. Results Following stereotaxic injection into the adult mouse hippocampus, titer-adjusted lentiviral vectors bearing constitutive promoters resulted in robust and sub-region-specific transgene expression. Our results show that the human CMV-IE promoter resulted in efficient transgene expression in the entire hippocampus whereas transgene expression mediated by the hybrid hEF1,/HTLV promoter was limited mainly in the dentate gyrus and the CA2/3 region. Finally, the neuron-specific human synapsin I promoter was particularly effective in the dentate gyrus. Conclusions These findings indicate that subregion-specific transgene expression in the hippocampus can be achieved following lentivirus vector-mediated gene transfer. Copyright © 2008 John Wiley & Sons, Ltd. [source] Agonistic behavior and electrical stimulation of the antennae induces Fos-like protein expression in the male cricket brainARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 1 2010Kaushik Ghosal Abstract Immediate early genes (IEG) such as c-Fos and Fos-related antigens (FRA) have been used as markers of neuronal activation. In this study, we determined whether the expression of c-Fos/FRAs is increased in the brains of adult male Acheta domesticus crickets following agonistic interactions. We looked for c-Fos/FRA proteins in the brain of un-fought, control male crickets and of dominant and subordinate male crickets sacrificed at different time periods following an agonistic interaction. Using immunoblot analysis, we found four different c-Fos/FRA-like proteins in the adult cricket brain. Continuous agonistic interaction increased c-Fos/FRA protein expression in the brains of subordinate males compared to control and dominant males. In addition, direct electrical stimulation of the male cricket antennae increased c-Fos/FRA-like protein in the brain. We identified the specific brain regions that exhibit c-Fos/FRA-like immunoreactivity in crickets. We detected c-Fos/FRA-like cellular immunoreactivity in different functional regions of the adult brain including the pars intercerebralis, protocerebrum, deutocerebrum, and the cortex of the mushroom bodies. © 2010 Wiley Periodicals, Inc. [source] Neuroprotective effect of chronic lithium treatment against hypoxia in specific brain regions with upregulation of cAMP response element binding protein and brain-derived neurotrophic factor but not nerve growth factor: comparison with acute lithium treatmentBIPOLAR DISORDERS, Issue 3 2008N Omata Objectives:, We evaluated the neuroprotective effect of chronically or acutely administered lithium against hypoxia in several brain regions. Furthermore, we investigated the contribution of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and cAMP response element binding protein (CREB) to the neuroprotective effect of lithium. Methods:, Brain slices were prepared from rats that had been treated chronically or acutely with lithium. The cerebral glucose metabolic rate (CMRglc) before and after hypoxia loading to brain slices was measured using the dynamic positron autoradiography technique with [18F]2-fluoro-2-deoxy- d -glucose. The changes of expression of proteins were investigated using Western blot analysis. Results:, Before hypoxia loading, the CMRglc did not differ between the lithium-treated and untreated groups. After hypoxia loading, the CMRglc of the untreated group was significantly lower than that before hypoxia loading. However, the CMRglc of the chronic lithium treatment group recovered in the frontal cortex, caudate putamen, hippocampus and cerebellum, but not in the thalamus. In contrast, the CMRglc of the acute lithium treatment group did not recover in any analyzed brain regions. After chronic lithium treatment, the levels of expression of BDNF and phospho-CREB were higher than those of untreated rats in the frontal cortex, but not in the thalamus. However, the expression of NGF did not change in the frontal cortex and thalamus. Conclusions:, These results demonstrated that lithium was neuroprotective against hypoxia only after chronic treatment and only in specific brain regions, and that CREB and BDNF might contribute to this effect. [source] | ||||||||||||||||