Neuroscience
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Chronic exposure to stress hormones has an impact on brain structures relevant to cognition. Nicotinic acetylcholine receptors (AChRs) are involved in numerous cognitive processes including learning and memory formation. In order to better understand the molecular mechanisms of chronic stress-triggered mental disease, the effect of corticosterone (CORT) on the biology of AChRs was studied in the neuronal cell line CNh. ⋯ Overexpression of α7-AChR-GFP abolished the CORT effects on the cell cycle and the specific α7-AChR inhibitor, methyllycaconitine, mimicked the proliferative action exerted by CORT. Whole-cell voltage-clamp recordings showed a significant decrease in nicotine-evoked currents in CORT-treated cells. Taken together, these observations indicate that AChRs, and the α7-AChR in particular, could act as modulators of the differentiation of CNh cells and that CORT could impair the acquisition of a mature phenotype by affecting the function of this AChR subtype.
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We have previously shown near infrared light (NIr), directed transcranially, mitigates the loss of dopaminergic cells in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice, a model of parkinsonism. These findings complement others suggesting NIr treatment protects against damage from various insults. However one puzzling feature of NIr treatment is that unilateral exposure can lead to a bilateral healing response, suggesting NIr may have 'indirect' protective effects. ⋯ Astrocyte and microglia cell numbers in substantia nigra pars compacta were not influenced by either mode of NIr treatment. In summary, the findings suggest that treatment of a remote tissue with NIr is sufficient to induce protection of the brain, reminiscent of the 'abscopal effect' sometimes observed in radiation treatment of metastatic cancer. This discovery has implications for the clinical translation of light-based therapies, providing an improved mode of delivery over transcranial irradiation.
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Accumulating evidence suggested that hyperglycemia played a critical role in hippocampus dysfunction in patients with diabetes mellitus. However, the multifactorial pathogenesis of hyperglycemia-induced impairments of hippocampal neurons has not been fully elucidated. Docosahexaenoic acid (DHA) has been shown to enhance learning and memory and affect neural function in various experimental conditions. ⋯ DHA treatment reduced oxidative stress and TNF-α expression, protected the hippocampal neurons by increasing AKT phosphorylation and decreasing caspase-3 and caspase-9 expression. These results suggested that high-glucose exposure induced injury of hippocampal neurons in vitro, and the principle mechanisms involved in the neuroprotective effect of DHA were its antioxidant and anti-apoptotic potential. DHA may thus be of use in preventing or treating neuron-degeneration resulting from hyperglycemia.
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Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by overactivity, impulsiveness and attentional problems, including an increase in distractibility. A structure that is intimately linked with distractibility is the superior colliculus (SC), a midbrain sensory structure which plays a particular role in the production of eye and head movements. Although others have proposed the involvement of such diverse elements as the frontal cortex and forebrain noradrenaline in ADHD, given the role of the colliculus in distractibility and the increased distractibility in ADHD, we have proposed that distractibility in ADHD arises due to collicular sensory hyper-responsiveness. ⋯ It also reduced the peak amplitude and summed activity of the multi-unit response in GH animals, at higher doses bringing it down to levels that were equivalent to those of Wistar animals at baseline. The present results provide convergent evidence that a collicular dysfunction (sensory hyper-responsiveness) is present in ADHD, and that it may underlie the enhanced distractibility. In addition, D-amphetamine - a widely used treatment in ADHD - may have one of its loci of therapeutic action at the level of the colliculus.
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Interleukin (IL)-17A plays an important role in the cerebral ischemia/reperfusion (I/R) injury. However, the mechanisms are still largely unknown. Calpain-transient receptor potential canonical (subtype) 6 (TRPC6) signaling pathway has been recently found to be implicated in brain I/R injury. ⋯ Recombinant IL-17A treatment markedly increased I/R injury. In conclusion, IL-17A may promote brain I/R injury through the increase of calpain-mediated TRPC6 proteolysis. These results further outline a novel neuroprotective strategy with increased effectiveness for the inhibition of excess brain IL-17A in cerebral I/R injury.