Neuroscience
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Absence seizures are known to result from disturbances within the cortico-thalamocortical network, which remains partially synchronous under normal conditions but switches to a state of hypersynchronicity and hyperexcitability during absence seizures. There is evidence to suggest that impaired GABAergic inhibitory function within the thalamus could contribute to the generation of hypersynchronous oscillations in some animal models of absence epilepsy. Recently, we demonstrated region-specific alterations in the tissue expression level of GABAA receptors (GABA(A)Rs) α1 and β2 subunits within the thalamus of the stargazer mouse model of absence epilepsy. ⋯ Furthermore, we investigated whether tissue expression of GABA(A)R subunits α4 and δ, which constitute part of tonic GABA(A)Rs in the VP region, is altered in the stargazer mouse. Semi-quantitative Western blotting showed a significant increase in GABA(A)R α4 and δ subunits in the VP region of stargazer thalamus, which would indicate an increase in tonic GABA(A)R expression. Our findings show that there are changes in the levels of both phasic and tonic GABA(A)Rs in the VP thalamus; altered GABAergic inhibition within the VP could be one of many mechanisms contributing to the generation of absence seizures in this model.
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Acidic fibroblast growth factor (aFGF) is a neurotrophic factor which is a powerful neuroprotective and neuroregenerative factor of the nervous system. Prior study had shown that levels of FGFs significantly increase following ischemic injury, reflecting a physiological protection mechanism. However, few reports demonstrated the efficacy of applying aFGF in cerebral ischemia. ⋯ In addition, topical application of fibrin glue-mixed aFGF dose-dependently reduced ischemia-induced brain infarction and improved functional restoration in ischemic stroke rats. Slow-released aFGF not only protected hippocampal and cortical cell loss but reduced microglial infiltration in FCI rats. Our results suggest that aFGF mixed in fibrin glue could prolong the protective/regenerative efficacy of aFGF to the damaged brain tissue and thus improve the functional restorative effect of aFGF.
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The clinical differential diagnosis between the Parkinson variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD) is difficult in early stages. To identify objective markers for differential diagnosis, we combined the novel tract-based spatial statistics (TBSS) and region of interest (ROI) analyses for the first time to investigate three groups (15 MSA-P, 20 PD patients and 20 controls) with diffusion tensor imaging data. By TBSS, we performed pairwise comparisons of fractional anisotropy (FA), mean diffusivity, radial diffusivity (RD) and axial diffusivity maps. ⋯ FA/RD values in bilateral corticospinal tract (CST) and left anterior thalamic radiation (ATR) in MSA-P were significantly different from PD or controls, and significantly correlated with clinical data. These findings indicated that the abnormalities of left ATR and bilateral CST were specific for MSA-P relative to PD or controls, and seemed to be promising for differential diagnosis. Furthermore, it may be useful for severity assessment of MSA-P.
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Spatial orientation and navigation depends on information from the vestibular system. Previous work suggested impaired spatial navigation in patients with bilateral vestibular failure (BVF). The aim of this study was to investigate event-related brain activity by functional magnetic resonance imaging (fMRI) during spatial navigation and visual memory tasks in BVF patients. ⋯ Cerebellar activity during spatial navigation in BVF patients may reflect increased non-vestibular efforts to counteract the development of spatial navigation deficits in BVF. Conceivably, cerebellar activity indicates a change in navigational strategy of BVF patients, i.e. from a more allocentric, landmark or place-based strategy (hippocampus) to a more sequence-based strategy. This interpretation would be in accord with recent evidence for a cerebellar role in sequence-based navigation.
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Allopregnanolone (APα; 5α-pregnan-3α-ol-20-one) is synthesized in both the periphery and central nervous system and is known to be a potent positive allosteric modulator of the GABAA receptor. Because APα was suggested to improve the symptoms of depression and Alzheimer's disease (AD), which involve synaptic dysfunction and loss, we examined whether APα affects excitatory synapses. Drebrin, which is an actin-binding protein, forms a unique stable actin structure in dendritic spines, and drebrin levels correlate positively with cognitive levels in AD and mild cognitive impairment. ⋯ Therefore, the PKA-cAMP response element-binding protein (CREB) signaling pathway is likely to be involved in the APα-induced increase of mature excitatory synapses. Another possibility is that the PKA-dependent increase in AMPA receptors at dendritic spines mediates the APα function. In conclusion, our study indicates that APα may improve neuropsychiatric disorder outcomes via increasing the numbers of mature excitatory synapses.