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Selected AbstractsGenetic Correlations Between Initial Sensitivity to Ethanol and Brain cAMP Signaling in Inbred and Selectively Bred MiceALCOHOLISM, Issue 6 2001Shelli L. Kirstein Background: Several lines of evidence have suggested a role for cAMP (adenosine 3,,5,-cyclic monophosphate) signaling in the acute and chronic effects of ethanol. This study investigated whether there is a genetic correlation between cAMP synthesis in the brain and the acute effects of ethanol [alcohol sensitivity or acute functional tolerance (AFT)]. Methods: By using nine inbred strains of mice, we measured initial sensitivity and AFT to ethanol with a test of balance on a dowel. Initial sensitivity was defined by the blood ethanol concentration (BEC0) at the loss of balance on a dowel after an ethanol injection [1.75 g/kg intraperitoneally (ip)]. When mice were able to regain balance on the dowel, BEC1 was determined, and a second ethanol injection was given (2 g/kg ip). Upon final regaining of balance, BEC2 was determined. AFT was defined by the difference between BEC1 and BEC2 (AFT =,BEC = BEC2, BEC1). Cyclic AMP synthesis was measured in whole-cell preparations in the cerebellum and other brain areas of mice of the nine inbred strains. Results: Significant differences in BEC0 and AFT were seen among the mice of the nine inbred strains. Cerebellar basal and forskolin- and isoproterenol-stimulated cAMP production differed significantly between the strains, and BEC0 was found to correlate significantly with forskolin- and isoproterenol-stimulated cAMP accumulation in the cerebellum (r= 0.70 and 0.94, respectively). When we measured cAMP production in mesencephalic and telencephalic tissue in three strains of mice that differed significantly in isoproterenol-stimulated cAMP accumulation in the cerebellum, significant differences between strains were found only in telencephalic tissue. The relative relationship between the rank order of the three strains for cAMP accumulation in the telencephalon and initial sensitivity to ethanol was identical to that seen with the cerebellum. However, AFT did not correlate with cAMP accumulation in the cerebellum or any other brain area tested. Conclusions: These results suggest that cAMP-generating systems of the cerebellum and possibly the brain areas contained in telencephalic tissues (e.g., basal ganglia) may have an important relationship to an animal's initial sensitivity to the incoordinating effects of ethanol. [source] The effects of social environment on adult neurogenesis in the female prairie voleDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2002Christie D. Fowler Abstract In the mammalian brain, adult neurogenesis has been found to occur primarily in the subventricular zone (SVZ) and dentate gyrus of the hippocampus (DG) and to be influenced by both exogenous and endogenous factors. In the present study, we examined the effects of male exposure or social isolation on neurogenesis in adult female prairie voles (Microtus ochrogaster). Newly proliferated cells labeled by a cell proliferation marker, 5-bromo-2,-deoxyuridine (BrdU), were found in the SVZ and DG, as well as in other brain areas, such as the amygdala, hypothalamus, neocortex, and caudate/putamen. Two days of male exposure significantly increased the number of BrdU-labeled cells in the amygdala and hypothalamus in comparison to social isolation. Three weeks later, group differences in BrdU labeling generally persisted in the amygdala, whereas in the hypothalamus, the male-exposed animals had more BrdU-labeled cells than did the female-exposed animals. In the SVZ, 2 days of social isolation increased the number of BrdU-labeled cells compared to female exposure, but this difference was no longer present 3 weeks later. We have also found that the vast majority of the BrdU-labeled cells contained a neuronal marker, indicating neuronal phenotypes. Finally, group differences in the number of cells undergoing apoptosis were subtle and did not seem to account for the observed differences in BrdU labeling. Together, our data indicate that social environment affects neuron proliferation in a stimulus- and site-specific manner in adult female prairie voles. © 2002 Wiley Periodicals, Inc. J Neurobiol 51: 115,128, 2002 [source] Changes in NOS protein expression and activity in the rat hippocampus, entorhinal and postrhinal cortices after unilateral electrolytic perirhinal cortex lesionsHIPPOCAMPUS, Issue 5 2003Ping Liu Abstract The integrity of the perirhinal cortex is critical for certain types of learning and memory. One important issue relating to the function of this region is its interaction with other brain areas that play a role in memory processing. This study investigates the time course of changes in activity and protein expression of nitric oxide synthase (NOS), which transforms L -arginine into nitric oxide (NO) and citrulline, in the hippocampus and the entorhinal and postrhinal cortices after unilateral electrolytic lesions of the perirhinal cortex. Electrolytic lesions of the perirhinal cortex resulted in long lasting changes in NOS activity and protein expression in the entorhinal and postrhinal cortices (,2 weeks post-lesion). In contrast, there was a small and transient decrease in nNOS expression (with no change in NOS activity) in the dorsal portion of the hippocampus. iNOS was not expressed in any region examined at any time point. These findings provide the first evidence that electrolytic lesions of the perirhinal cortex can result in long-term neurochemical changes in its anatomically related structures. Given that NO has been implicated in neuroplasticity processes, the interpretation of memory impairments induced by electrolytic lesions of the perirhinal cortex (and possibly, therefore, other brain regions) need to be considered with regard to these findings. Hippocampus 2003;13:561,571. © 2003 Wiley-Liss, Inc. [source] Genetic influences on human brain structure: A review of brain imaging studies in twins,HUMAN BRAIN MAPPING, Issue 6 2007Jiska S. Peper Abstract Twin studies suggest that variation in human brain volume is genetically influenced. The genes involved in human brain volume variation are still largely unknown, but several candidate genes have been suggested. An overview of structural Magnetic Resonance (brain) Imaging studies in twins is presented, which focuses on the influence of genetic factors on variation in healthy human brain volume. Twin studies have shown that genetic effects varied regionally within the brain, with high heritabilities of frontal lobe volumes (90,95%), moderate estimates in the hippocampus (40,69%), and environmental factors influencing several medial brain areas. High heritability estimates of brain structures were revealed for regional amounts of gray matter (density) in medial frontal cortex, Heschl's gyrus, and postcentral gyrus. In addition, moderate to high heritabilities for densities of Broca's area, anterior cingulate, hippocampus, amygdala, gray matter of the parahippocampal gyrus, and white matter of the superior occipitofrontal fasciculus were reported. The high heritability for (global) brain volumes, including the intracranium, total brain, cerebral gray, and white matter, seems to be present throughout life. Estimates of genetic and environmental influences on age-related changes in brain structure in children and adults await further longitudinal twin-studies. For prefrontal cortex volume, white matter, and hippocampus volumes, a number of candidate genes have been identified, whereas for other brain areas, only a few or even a single candidate gene has been found so far. New techniques such as genome-wide scans may become helpful in the search for genes that are involved in the regulation of human brain volume throughout life. Hum Brain Mapp, 2007. © 2007 Wiley-Liss, Inc. [source] Restricted, but abundant, expression of the novel rat gene-3 (R3) relaxin in the dorsal tegmental region of brainJOURNAL OF NEUROCHEMISTRY, Issue 6 2002Tanya C. D. Burazin Abstract Relaxin is a peptide hormone with known actions associated with female reproductive physiology, but it has also been identified in the brain. Only one relaxin gene had been characterized in rodents until recently when a novel human relaxin gene, human gene-3 (H3) and its mouse equivalent (M3) were identified. The current study reports the identification of a rat homologue, rat gene-3 (R3) relaxin that is highly expressed in a discrete region of the adult brain. The full R3 relaxin cDNA was generated using RT-PCR and 3, and 5, RACE protocols. The derived amino acid sequence of R3 relaxin retains all the characteristic features of a relaxin peptide and has a high degree of homology with H3 and M3 relaxin. The distribution of R3 relaxin mRNA in adult rat brain was determined and highly abundant expression was only detected in neurons of the ventromedial dorsal tegmental nucleus (vmDTg) in the pons, whereas all other brain areas were unlabelled or contained much lower mRNA levels. Relaxin binding sites and relaxin immunoreactivity were also detected in the vmDTg. These together with earlier findings provide strong evidence for a role(s) for multiple relaxin peptides as neurotransmitters and/or modulators in the rat CNS. [source] Postnatal development of 11,-hydroxysteroid dehydrogenase type 1 in the rat hippocampusJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2002S.L. Wan Abstract Glucocorticoids (GCs) have important actions in the hippocampus of the brain, where their access to glucocorticoid receptor (GR) is increased by 11,-hydroxysteroid dehydrogenase type 1 (11,-HSD1). 11,-HSD1 converts biologically inactive 11-dehydrocorticosterone into active corticosterone. However, the postnatal development of 11,-HSD1 in the hippocampus is not properly understood. In this study, the postnatal distribution and development of 11,-HSD1 in the hippocampus of the rat brain was studied with immunohistochemistry and Western blot analysis. Results showed that abundant 11,-HSD1 immunoreactive substance (ir-11,-HSD1) was present in the hippocampus. There were homogeneous distributions of 11,-HSD1 in the hippocampal CA1, CA2, CA3, CA4 regions and the dentate gyrus at postnatal days 1, 3, and 7. Interestingly, the developmental distribution of GR in the hippocampus followed the same pattern as 11,-HSD1. Western blot analysis demonstrated that a higher level of expression of 11,-HSD1 in the hippocampus was found in the first 2 weeks of life. The expressions of 11,-HSD1 started to drop to adult levels at about postnatal day 15 both in the hippocampus and in other brain areas. These results suggest that the higher expression of 11,-HSD1 in the neonatal hippocampus may be important for the maturation of the central nervous system mediated by GCs through GR. © 2002 Wiley-Liss, Inc. [source] Neuroadaptations of Cdk5 in Cholinergic Interneurons of the Nucleus Accumbens and Prefrontal Cortex of Inbred Alcohol-preferring Rats Following Voluntary Alcohol DrinkingALCOHOLISM, Issue 8 2006Marguerite Charlotte Camp Background: Neurobiological studies have identified brain areas and related molecular mechanisms involved in alcohol abuse and dependence. Specific cell types in these brain areas and their role in alcohol-related behaviors, however, have not yet been identified. This study examined the involvement of cholinergic cells in inbred alcohol-preferring rats following 1 month of alcohol drinking. Cyclin-dependent kinase 5 (Cdk5) immunoreactivity (IR), a marker of neuronal plasticity, was examined in cholinergic neurons of the nucleus accumbens (NuAcc) and prefrontal cortex (PFC) and other brain areas implicated in alcohol drinking, using dual immunocytochemical (ICC) procedures. Single Cdk5 IR was also examined in several brain areas implicated in alcohol drinking. Methods: The experimental group self-administered alcohol using a 2-bottle-choice test paradigm with unlimited access to 10% (v/v) alcohol and water for 23 h/d for 1 month. An average of 6 g/kg alcohol was consumed daily. Control animals received identical treatment, except that both bottles contained water. Rats were perfused and brain sections were processed for ICC procedures. Results: Alcohol drinking resulted in a 51% increase in Cdk5 IR cholinergic interneurons in the shell NuAcc, while in the PFC there was a 51% decrease in the percent of Cdk5 IR cholinergic interneurons in the infralimbic region and a 46% decrease in Cdk5 IR cholinergic interneurons in the prelimbic region. Additionally, single Cdk5 IR revealed a 42% increase in the central nucleus of the amygdala (CNA). Conclusions: This study identified Cdk5 neuroadaptation in cholinergic interneurons of the NuAcc and PFC and in other neurons of the CNA following 1 month of alcohol drinking. These findings contribute to our understanding of the cellular and molecular basis of alcohol drinking and toward the development of improved region and cell-specific pharmacotherapeutic and behavioral treatment programs for alcohol abuse and alcoholism. [source] Genetic Correlations Between Initial Sensitivity to Ethanol and Brain cAMP Signaling in Inbred and Selectively Bred MiceALCOHOLISM, Issue 6 2001Shelli L. Kirstein Background: Several lines of evidence have suggested a role for cAMP (adenosine 3,,5,-cyclic monophosphate) signaling in the acute and chronic effects of ethanol. This study investigated whether there is a genetic correlation between cAMP synthesis in the brain and the acute effects of ethanol [alcohol sensitivity or acute functional tolerance (AFT)]. Methods: By using nine inbred strains of mice, we measured initial sensitivity and AFT to ethanol with a test of balance on a dowel. Initial sensitivity was defined by the blood ethanol concentration (BEC0) at the loss of balance on a dowel after an ethanol injection [1.75 g/kg intraperitoneally (ip)]. When mice were able to regain balance on the dowel, BEC1 was determined, and a second ethanol injection was given (2 g/kg ip). Upon final regaining of balance, BEC2 was determined. AFT was defined by the difference between BEC1 and BEC2 (AFT =,BEC = BEC2, BEC1). Cyclic AMP synthesis was measured in whole-cell preparations in the cerebellum and other brain areas of mice of the nine inbred strains. Results: Significant differences in BEC0 and AFT were seen among the mice of the nine inbred strains. Cerebellar basal and forskolin- and isoproterenol-stimulated cAMP production differed significantly between the strains, and BEC0 was found to correlate significantly with forskolin- and isoproterenol-stimulated cAMP accumulation in the cerebellum (r= 0.70 and 0.94, respectively). When we measured cAMP production in mesencephalic and telencephalic tissue in three strains of mice that differed significantly in isoproterenol-stimulated cAMP accumulation in the cerebellum, significant differences between strains were found only in telencephalic tissue. The relative relationship between the rank order of the three strains for cAMP accumulation in the telencephalon and initial sensitivity to ethanol was identical to that seen with the cerebellum. However, AFT did not correlate with cAMP accumulation in the cerebellum or any other brain area tested. Conclusions: These results suggest that cAMP-generating systems of the cerebellum and possibly the brain areas contained in telencephalic tissues (e.g., basal ganglia) may have an important relationship to an animal's initial sensitivity to the incoordinating effects of ethanol. [source] Distribution Pattern of Neuropeptide Y in the Brain, Pituitary and Olfactory System during the Larval Development of the Toad Rhinella arenarum (Amphibia: Anura)ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2 2009T. Heer Summary The first NPY-immunoreactivity (ir) in the central nervous system of Rhinella arenarum was obtained just after hatching in the pre-optic area, ventral thalamus and rostral rhombencephalon. During pre-metamorphosis, new NPY-ir cells were observed in other brain areas such as pallium, septum and striatum, infundibulum and pars intermedia of the pituitary. Further maturation continued through pro-metamorphosis with the appearance of cell groups in the diagonal band, amygdala, pre-optic nucleus, dorsal nucleus of the habenula, anterior ventral and dorsal thalamus, suprachiasmatic nucleus, tuberculum posterior, tectum, torus semicircularis, inter-peduncular nucleus and median eminence. During the metamorphic climax and soon after, the relative abundance of NPY-ir fibres decreased in all hypothalamic areas and the staining intensity and number of NPY-ir cells in the pallium also decreased, whereas no cells were found in the striatum, dorsal nucleus of the habenula and tectum. In the olfactory epithelium, nerve or bulb, neither cells nor NPY-ir fibres were found during the stages of development analysed. The ontogeny pattern of the NPY-ir neuronal system in the brain of Rh. arenarum is more similar to the spatiotemporal appearance reported for Rana esculenta than to that reported for Xenopus laevis. Many NPY-ir fibres were found in the median eminence and in the pars intermedia of the pituitary, supporting the idea that this neuropeptide may play a role in the modulation of hypophyseal secretion during development. [source] Abnormal cerebellum density in victims of rape with post-traumatic stress disorder: Voxel-based analysis of magnetic resonance imaging investigationASIA-PACIFIC PSYCHIATRY, Issue 3 2010Shuang-Ge Sui MD MBA Abstract Introduction: Based on early studies of non-motor function in the cerebellum and dysfunction in the cerebellum of post-traumatic stress disorder (PTSD) patients, we presumed that the cerebellum was involved in the neuropathology of cognitive and emotional processing of PTSD patients, while the density of some sub-areas of the cerebellum of PTSD patients was most likely abnormal. Methods: Eleven female victims of rape with PTSD and 12 age-matched female normal controls received 1.5 T 3D magnetic resonance imaging (MRI) scan. The scans were then analyzed using the voxel-based morphometry 2 (VBM2) toolbox. Results: Victims of rape with PTSD showed increased cerebellum density on the left side compared with normal controls (P<0.001), especially in the pyramis (x=,9, y=,72, z=,36; k=519; t=4.70), uvula (x=,4, y=,66, z=,35; k=256; t=4.02), declive (x=,6, y=,69, z=,30; k=213; t=3.84) and nodule (x=,4, y=,63, z=,31; k=147; t=3.93). In addition, compared with normal controls, the PTSD group showed significant differences in gray matter density of other brain areas, including the frontal lobe, parietal lobe, occipital lobe (P<0.001), insula, posterior cingulate, amygdala and hippocampus (P<0.005). Discussion: These finding suggest that the cerebellum may be involved in the neuropathology and functional compensation in the neurocircuitry of PTSD. [source] Magnetic resonance spectroscopy in anxiety disordersACTA NEUROPSYCHIATRICA, Issue 2 2008Clarissa Trzesniak Objective:, Magnetic resonance spectroscopy (MRS) is a non-invasive in vivo method used to quantify metabolites that are relevant to a wide range of brain processes. This paper briefly describes neuroimaging using MRS and provides a systematic review of its application to anxiety disorders. Method:, A literature review was performed in the PubMed, Lilacs and Scielo databases using the keywords spectroscopy and anxiety disorder. References of selected articles were also hand-searched for additional citations. Results:, Recent studies have shown that there are significant metabolic differences between patients with anxiety disorders and healthy controls in various regions of the brain. Changes were mainly found in N -acetylaspartate, which is associated with neuronal viability, but some of them were also seen in creatine, a substance that is thought to be relatively constant among individuals with different pathological conditions. Conclusions:, MRS is a sophisticated neuroimaging technique that has provided useful insights into the biochemical and neurobiological basis of many anxiety disorders. Nevertheless, its utilization in some anxiety disorders is still modest, particularly social phobia and generalised anxiety. Although it is an extremely useful advance in neuroimaging, further research in other brain areas and patient populations is highly advisable. [source] |