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Central Nervous System Function (central + nervous_system_function)
Selected AbstractsStrain-dependent regulation of neurotransmission and actin-remodelling proteins in the mouse hippocampusGENES, BRAIN AND BEHAVIOR, Issue 2 2006D. D. Pollak Individual mouse strains differ significantly in terms of behaviour, cognitive function and long-term potentiation. Hippocampal gene expression profiling of eight different mouse strains points towards strain-specific regulation of genes involved in neuronal information storage. Protein expression with regard to strain- dependent expression of structures related to neuronal information storage has not been investigated yet. Herein, a proteomic approach based on two-dimensional gel electrophoresis coupled with mass spectrometry (MALDI-TOF/TOF) has been chosen to address this question by determining strain-dependent expression of proteins involved in neurotransmission and activity-induced actin remodelling in hippocampal tissue of five mouse strains. Of 31 spots representing 16 different gene products analysed and quantified, N -ethylmaleimide-sensitive fusion protein, N -ethylmaleimide-sensitive factor attachment protein-,, actin-like protein 3, profilin and cofilin were expressed in a strain-dependent manner. By treating protein expression as a phenotype, we have shown significant genetic variation in brain protein expression. Further experiments in this direction may provide an indication of the genetic elements that contribute to the phenotypic differences between the selected strains through the expressional level of the translated protein. In view of this, we propose that proteomic analysis enabling to concomitantly survey the expression of a large number of proteins could serve as a valuable tool for genetic and physiological studies of central nervous system function. [source] Altered Mesencephalic Dopaminergic Populations in Adulthood as a Consequence of Brief Perinatal Glucocorticoid ExposureJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2005S. McArthur Abstract Early exposure to stressors is strongly associated with enduring effects on central nervous system function, but the mechanisms and neural substrates involved in this biological ,programming' are unclear. This study tested the hypothesis that inappropriate exposure to glucocorticoid stress hormones (GCs) during critical periods of development permanently alters the mesencephalic dopaminergic populations in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Using a rat model, the synthetic GC dexamethasone was added to the maternal drinking water during gestational days 16,19 or over the first week of postnatal life. In adulthood, the effects upon tyrosine hydroxylase immunopositive (TH+) cell numbers in the midbrain, and monoamine levels in the forebrain, of the adult offspring were assessed and compared with control offspring whose dams received normal drinking water. In the VTA, both prenatal and postnatal dexamethasone treatment increased TH+ cell numbers by approximately 50% in males and females. Although prenatal dexamethasone treatment also increased TH+ cell numbers in the SNc by 40,50% in males and females, postnatal treatment affected females only by increasing TH+ cell numbers by approximately 30%. In comparison, similar changes were not detected in the monoamine levels of the dorsolateral striatum, nucleus accumbens or infralimbic cortex of either males or females, which is a feature likely to reflect adaptive changes in these pathways. These studies demonstrate that the survival or phenotypic expression of VTA and SNc dopaminergic neurones is profoundly influenced by brief perinatal exposure to GCs at times when endogenous levels are normally low. These findings are the first to demonstrate permanent changes in the cytoarchitecture within midbrain dopamine nuclei after perinatal exposure to stress hormones and implicate altered functionality. Thus, they have significance for the increasing use of GCs in perinatal medicine and indicate potential mechanisms whereby perinatal distress may predispose to the development of a range of psychiatric conditions in later life. [source] The unique value of primate models in translational researchAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009Carol A. Shively Abstract This special issue of AJP is focused on research using nonhuman primates as models to further the understanding of women's health. Nonhuman primates play a unique role in translational science by bridging the gap between basic and clinical investigations. The use of nonhuman primates in biomedical research challenges our resolve to treat all life as sacred. The scientific community has responded by developing ethical guidelines for the care and the use of primates and clarifying the responsibility of investigators to insure the physical and psychological well-being of nonhuman primates used in research. Preclinical investigations often involve the use of animal models. Rodent models have been the mainstay of biomedical science and have provided enormous insight into the workings of many mammalian systems that h ave proved applicable to human biological systems. Rodent models are dissimilar to primates in numerous ways, which may limit the generalizability to human biological systems. These limitations are much less likely in nonhuman primates and in Old World primates, in particular, Macaques are useful models for investigations involving the reproductive system, bioenergetics, obesity and diabetes, cardiovascular health, central nervous system function, cognitive and social behavior, the musculoskeletal system, and diseases of aging. This issue considers primate models of polycystic ovary syndrome; diet effects on glycemic control, breast and endometrium; estrogen, reproductive life stage and atherosclerosis; estrogen and diet effects on inflammation in atherogenesis; the neuroprotective effects of estrogen therapy; social stress and visceral obesity; and sex differences in the role of social status in atherogenesis. Unmet research needs in women's health include the use of diets in nonhuman primate studies that are similar to those consumed by human beings, primate models of natural menopause, dementia, hypertension, colon cancer, and frailty in old age, and dedicated colonies for the study of breast cancer. Am. J. Primatol. 71:715,721, 2009. © 2009 Wiley-Liss, Inc. [source] Effect of 1,,25-dihydroxyvitamin D3 in embryonic hippocampal cellsHIPPOCAMPUS, Issue 6 2010Francesca Marini Abstract Although the role of 1,,25-dihydroxyvitamin D3 in calcium homeostasis of bone tissue is clear, evidence of the involvement of vitamin D3 in the central nervous system functions is increasing. In fact, vitamin D3 regulates vitamin D receptor and nerve growth factor expression, modulates brain development, and reverses experimental autoimmune encephalomyelitis. Only few studies, however, address vitamin D3 effect on embryonic hippocampal cell differentiation. In this investigation, the HN9.10e cell line was used as experimental model; these cells, that are a somatic fusion product of hippocampal cells from embryonic day-18 C57BL/6 mice and N18TG2 neuroblastoma cells, show morphological and cytoskeletal features similar to their neuronal precursors. By this model, we have studied the time course of vitamin D3 localization in the nucleus and its effect on proteins involved in proliferation and/or differentiation. We found that the translocation of vitamin D3 from cytoplasm to the nucleus is transient, as the maximal nuclear concentration is reached after 10 h of incubation with 3H-vitamin D3 and decreases to control values by 12 h. The appearance of differentiation markers such as Bcl2, NGF, STAT3, and the decrease of proliferation markers such as cyclin-1 and PCNA are late events. Moreover, physiological concentrations of vitamin D3 delay cell proliferation and induce cell differentiation of embryonic cells characterized by modification of soma lengthening and formation of axons and dendrites. © 2009 Wiley-Liss, Inc. [source] Protective effects of melatonin against oxidative stress in Fmr1 knockout mice: a therapeutic research model for the fragile X syndromeJOURNAL OF PINEAL RESEARCH, Issue 2 2009Yanina Romero-Zerbo Abstract:, Fragile X syndrome is the most common form of inherited mental retardation. It is typically caused by a mutation of the Fragile X mental-retardation 1 (Fmr1) gene. To better understand the role of the Fmr1 gene and its gene product, the fragile X mental-retardation protein in central nervous system functions, an fmr1 knockout mouse that is deficient in the fragile X mental-retardation protein was bred. In the present study, fragile X mental retardation 1-knockout and wild-type mice are used to determine behaviour and oxidative stress alterations, including reduced glutathione, oxidized glutathione and thiobarbituric acid-reactive substances, before and after chronic treatment with melatonin or tianeptine. Reduced glutathione levels were reduced in the brain of fmr1-knockout mice and chronic melatonin treatment normalized the glutathione levels compared with the control group. Lipid peroxidation was elevated in brain and testes of fmr1-knockout mice and chronic melatonin treatment prevents lipid peroxidation in both tissues. Interestingly, chronic treatment with melatonin alleviated the altered parameters in the fmr1-knockout mice, including abnormal context-dependent exploratory and anxiety behaviours and learning abnormalities. Chronic treatment with tianeptine (a serotonin reuptake enhancer) did not normalize the behaviour in fmr1-knockout mice. The prevention of oxidative stress in the fragile X mouse model, by an antioxidant compound such as melatonin, emerges as a new and promising approach for further investigation on treatment trials for the disease. [source] Onset of Kleine-Levin Syndrome in association with isotretinoin treatmentACTA PAEDIATRICA, Issue 6 2010H Smedje Abstract The synthetic retinoid isotretinoin is an effective treatment option for severe forms of acne vulgaris. However, several reports indicate that some patients experience altered central nervous system functions in association with treatment. We present here the first description of the onset of Kleine-Levin Syndrome (KLS), a rare disorder characterised by periodic hypersomnia and cognitive and behavioural symptoms, in close temporal relation to the start of isotretinoin treatment. We also discuss the biological potential of retinoids to affect sleep. Conclusions:, In light of a documented potential of retinoids to modulate sleep-wake regulation, the present case suggests that isotretinoin may rarely trigger the onset of KLS. [source] | |||||||||||||