Brain : a journal of neurology
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The natural history of brain growth in autism spectrum disorders remains unclear. Cross-sectional studies have identified regional abnormalities in brain volume and cortical thickness in autism, although substantial discrepancies have been reported. Preliminary longitudinal studies using two time points and small samples have identified specific regional differences in cortical thickness in the disorder. ⋯ Differences in age-related trajectories emerged in bilateral parietal and occipital regions (postcentral gyrus, cuneus, lingual gyrus, pericalcarine cortex), left frontal regions (pars opercularis, rostral middle frontal and frontal pole), left supramarginal gyrus, and right transverse temporal gyrus, superior parietal lobule, and paracentral, lateral orbitofrontal, and lateral occipital regions. We suggest that abnormal cortical development in autism spectrum disorders undergoes three distinct phases: accelerated expansion in early childhood, accelerated thinning in later childhood and adolescence, and decelerated thinning in early adulthood. Moreover, cortical thickness abnormalities in autism spectrum disorders are region-specific, vary with age, and may remain dynamic well into adulthood.
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Carpal tunnel syndrome, a median nerve entrapment neuropathy, is characterized by sensorimotor deficits. Recent reports have shown that this syndrome is also characterized by functional and structural neuroplasticity in the primary somatosensory cortex of the brain. However, the linkage between this neuroplasticity and the functional deficits in carpal tunnel syndrome is unknown. ⋯ Moreover, the second/third interdigit cortical separation distance was negatively correlated with paraesthesia severity (r = -0.31, P < 0.05), and number of pinch/release cycles (r = -0.31, P < 0.05), and positively correlated with the second and third digit sensory discrimination accuracy (r = 0.50, P < 0.05). Therefore, reduced second/third interdigit cortical separation distance in contralateral primary somatosensory cortex was associated with worse symptomatology (particularly paraesthesia), reduced fine motor skill performance, and worse sensory discrimination accuracy for median nerve innervated digits. In conclusion, primary somatosensory cortex neuroplasticity for median nerve innervated digits in carpal tunnel syndrome is indeed maladaptive and underlies the functional deficits seen in these patients.
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We have previously shown that crushing the optic nerve induces death of retinal ganglion cells by apoptosis, but suppression of CASP2, which is predominantly activated in retinal ganglion cells, using a stably modified short interfering RNA CASP2, inhibits retinal ganglion cell apoptosis. Here, we report that combined delivery of short interfering CASP2 and inhibition of CASP6 using a dominant negative CASP6 mutant activates astrocytes and Müller cells, increases CNTF levels in the retina and leads to enhanced retinal ganglion cell axon regeneration. In dissociated adult rat mixed retinal cultures, dominant negative CASP6 mutant + short interfering CASP2 treatment also significantly increases GFAP+ glial activation, increases the expression of CNTF in culture, and subsequently increases the number of retinal ganglion cells with neurites and the mean retinal ganglion cell neurite length. ⋯ Similarly, in the optic nerve crush injury model, MAB228 and AG490 neutralizes dominant negative CASP6 mutant + short interfering CASP2-mediated retinal ganglion cell axon regeneration, Müller cell activation and CNTF production in the retina without affecting retinal ganglion cell survival. We therefore conclude that axon regeneration promoted by suppression of CASP2 and CASP6 is CNTF-dependent and mediated through the JAK/STAT signalling pathway. This study offers insights for the development of effective therapeutics for promoting retinal ganglion cell survival and axon regeneration.
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Gaucher disease is caused by mutations in the glucocerebrosidase gene, which encodes the lysosomal hydrolase glucosylceramidase. Patients with Gaucher disease and heterozygous glucocerebrosidase mutation carriers are at increased risk of developing Parkinson's disease. Indeed, glucocerebrosidase mutations are the most frequent risk factor for Parkinson's disease in the general population. ⋯ In conclusion, glucocerebrosidase mutations are associated with reductions in glucosylceramidase activity and evidence of oxidative stress. Ambroxol treatment significantly increases glucosylceramidase activity and reduces markers of oxidative stress in cells bearing glucocerebrosidase mutations. We propose that ambroxol hydrochloride should be further investigated as a potential treatment for Parkinson's disease.