Neuroscience
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Depression induced by stress is affected by sex, age and hormonal status of the animal and also by duration and type of the stressors. Moreover, higher prevalence of depression and comorbidities in women than men implies the need to include the sex variable in studies on animal models of depression. The present study was therefore initiated to evaluate the effect of sex and ovarian hormones on depression-like phenotypes in mice exposed to a 21-day Chronic Variable Mild Stress (CVMS) paradigm. ⋯ There was a significant decrease in the BDNF protein expression along with an increase in the mRNA expression of CRH, NR3C1, CART, and NPY in intact females, but not in the other two groups of mice. OVX females resembled males in behavioral and molecular responses to CVMS. 17β-Estradiol (E2) administration, not Progesterone (P4), to OVX female stress mice, mitigated despair and enhanced hedonic capacity with an increased expression of BDNF in PFC. This study strengthens the evidence for the beneficial effects of E2 administration in stress condition.
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From a view point of the glutamate excitotoxicity theory, several studies have suggested that abnormal glutamate homeostasis via dysfunction of glial glutamate transporter-1 (GLT-1) may underlie neurodegeneration in amyotrophic lateral sclerosis (ALS). However, the detailed role of GLT-1 in the pathogenies of ALS remains controversial. To assess this issue, here we elucidated structural alterations associated with dysregulation of glutamate homeostasis using SOD1(G93A) mice, a genetic model of familial ALS. ⋯ Interestingly, the coverage of α-motoneurons by VGluT2(+) presynaptic terminals was transiently increased at 9weeks of age, and then gradually decreased towards 21weeks of age. On the other hand, there were no time-dependent alterations in the coverage of α-motoneurons by GABAergic presynaptic terminals. These findings suggest that VGluT2 and GLT-1 may be differentially involved in the pathogenesis of ALS via abnormal glutamate homeostasis at the presymptomatic stage and end stage of disease, respectively.
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The aim of the present study was to examine the modification of postural symmetry during quiet standing using a sensorimotor adaptation paradigm. A group of neurologically typical adult participants performed a visually guided mediolateral (left-right) weight shifting task requiring precise adjustments in body orientation. ⋯ COP during quiet standing without visual feedback was examined prior to and immediately following the sensorimotor adaptation procedure, in order to observe whether compensatory adjustments in postural control resulting from the visual-feedback manipulation would transfer to the control of whole-body COP during quiet standing. Results showed that the sensorimotor adaptation procedure induced a small but reliable compensatory change in the stance of participants, resulting in a change in postural symmetry and control that was found to persist even after normal visual feedback was restored.
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Neuroinflammation is a key component of the pathophysiology of neurodegenerative diseases. The link between nicotine intake and positive outcome has been established, suggesting a role played by nicotinic receptors (nAChRs), especially α7nAChRs. The objective of this study was to evaluate the potential dose effects of PHA 543613 on neuron survival and striatal microglial activation in a rat model of brain excitotoxicity. ⋯ We demonstrated that [3H]DPA-714 provides a better signal-to-noise ratio than [3H]PK-11195. Furthermore, we showed that repeated PHA 543613 administration at a dose of 12mg/kg to QA-lesioned rats significantly protected neurons and reduced the intensity of microglial activation. This study reinforces the hypothesis that α7nAChR agonists can provide beneficial effects in the treatment of neurodegenerative diseases through potential modulation of microglial activation.
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The study was undertaken to explore the cell-specific streptozotocin (STZ)-induced mechanistic alterations. STZ-induced rodent model is a well-established experimental model of Alzheimer's disease (AD) and in our previous studies we have established it as an in vitro screening model of AD by employing N2A neuronal cells. Therefore, STZ was selected in the present study to understand the STZ-induced cell-specific alterations by utilizing neuronal N2A and astrocytes C6 cells. ⋯ The cellular communication of astrocytes and neurons was altered as reflected by increased expression of connexin 43 along with DNA fragmentation. STZ-induced apoptotic death was evaluated by elevated expression of caspase-3 and PI/Hoechst staining of cells. In conclusion, study showed that STZ exert alike biochemical alterations, ER stress and cellular apoptosis in both neuronal and astrocyte cells.