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.