Neuroscience
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Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder affecting nearly one in 5000 newborn males and is a leading genetic cause of autism spectrum disorder. In addition to developmental delays and intellectual impairment, FXS is characterized by seizures, attention deficit, and hypersensitivity to visual, tactile and auditory stimuli. The Fmr1 gene encodes Fragile X mental retardation protein (FMRP), which is abundant in neurons, binds select mRNAs and functions as a negative regulator of mRNA translation. ⋯ Additionally, neurons in the medial superior olive (MSO) were more round in Fmr1 KO rats. There was also reduced expression of glutamic acid decarboxylase (GAD67) in neurons of the superior paraolivary nucleus (SPON) and a reduction in the number of calretinin-immunoreactive terminals associated with neurons of the medial nucleus of the trapezoid body (MNTB). Together, these findings support the conclusion that the auditory dysfunction characteristic of FXS arises, at least in part, from defective brainstem networks.
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Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive cell loss in the striatum and cerebral cortex, leading to a decline in motor control and eventually death. The mechanisms promoting motor dysfunction are not known, however loss of mitochondrial function and content has been observed, suggesting that mitochondrial dysfunction may contribute to HD phenotype. Recent work has demonstrated that voluntary wheel running reduces hindlimb clasping in the R6/1 mouse model of HD, which we hypothesized may be due to preservation of mitochondrial content with exercise. ⋯ At 27 wks of age, R6/1 mice demonstrated no additional changes in mitochondrial content or respiration within the cortex, but displayed loss of protein in complexes I and III of the striatum, which was not present in exercise-trained R6/1 mice. Mitochondrial respiration was also elevated in the striatum of R6/1 mice at 27 wks, which was prevented with exercise training. Together, the present study provides evidence that mitochondrial dysfunction is not necessary for the progression of hindlimb clasping in R6/1 mice, and that exercise partially prevents changes in mitochondrial content and function that occur late in HD.
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Schizophrenia is a devastating mental illness. Although its etiology is still largely unknown, strides have been taken throughout the last several decades to elucidate the nature of the neuropathology behind this disorder. The advent of neuroimaging technologies such as computerized axial tomography and magnetic resonance imaging have progressed knowledge about the macroscopic brain changes that occur in schizophrenia, including the characteristic enlarged ventricle size and reductions in gray matter volume, whole-brain volume, and white matter anisotropy. ⋯ This is consistent with neuroimaging data and implicates an altered aging trajectory as a factor in the pathogenesis of schizophrenia. Combined with evidence from other neuroanatomical studies reviewed here, as well as studies in childhood-onset schizophrenia, the evidence converges on a progressive neurodevelopmental model of schizophrenia related to altered neuroplasticity. The evidence also supports a particular vulnerability of inhibitory cortical circuits with markers of interneurons showing some of the more consistent reductions in schizophrenia.
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Traditionally, multiple sclerosis (MS) is considered to be a disease primarily affecting the white matter (WM). However, the development of some clinical symptoms such as cognitive impairment cannot be fully explained by the severity of WM pathology alone. During the past decades it became clear that gray matter (GM) damage of the brain is also of major importance in patients with MS. ⋯ However, despite these improvements, visualization of cortical MS lesions remains difficult (only about 30-50% of histopathologically confirmed lesions can be detected at 7 Tesla magnetic resonance imaging (MRI)). Furthermore, more research is needed to understand the exact interplay of cortical lesions, GM atrophy and WM pathology in the development of clinical symptoms. In this review, we summarize the historical background that preceded current research and provide an overview of the current knowledge on clinical consequences of GM pathology in MS in terms of disability, cognitive impairment and other clinically important signs such as epileptic seizures.
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Peripheral neuropathy is a major complication associated with diabetes and central neuropathy characterized by Alzheimer's disease-like features in the brain is associated with increased dementia risk for patients with diabetes. Although glucose uptake into the cells of the nervous system is insulin-independent, contribution of impaired insulin support is clearly recognized to play a role, however not yet fully understood, in the development of neuropathy. In this study, we assessed the direct role of insulin on the peripheral nervous system (PNS) and central nervous system (CNS) of insulin-dependent type 1 diabetic rats. ⋯ Both the sciatic nerve and hippocampus from type 1 diabetic rats were highly responsive to exogenous insulin with a significantly increased phosphorylation of insulin receptor and GSK3 compared to tissues from control rats. Further, sustained in vivo insulin delivery, not sufficient to restore normal blood glucose, normalized the activation of both insulin receptor and GSK3 in both PNS and CNS tissues. These results suggest that the insulin-signaling pathway is responsive to exogenous insulin in the nervous system of insulin-deficient type 1 diabetic rats and that constant insulin delivery restore normal nerve function and may protect PNS and CNS from damage.