Neuroscience
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When comparing motor performance of the dominant and nondominant hands, older adults tend to be less asymmetric compared to young adults. This has suggested decreased motor lateralization and functional compensation within the aging brain. ⋯ Using two naturalistic tasks that selectively biased the dominant or nondominant hands, we compared asymmetries in performance (measured as a ratio) across chronological age. Results showed preserved motor asymmetry across ages in both tasks, with no difference in asymmetry ratios in the 'old old' compared to the 'young old.' In the context of previous work, our findings suggest that the aging brain may also be characterized by additional measures besides chronological age.
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Serotonin (5-HT) is a key regulator of mood and sexual behaviors. 5-HT reuptake inhibitors have been used as antidepressants. Really interesting new gene (RING) finger proteins have been associated with 5-HT regulation but their role remains largely unknown. Some RING finger proteins are involved in the serotonergic system, therefore, we speculate that the gene expression of RING finger protein38 (rnf38) is regulated by the serotonergic system. ⋯ On the other hand, rnf38 gene was significantly high (P<0.05) in the telencephalon and the hypothalamus. This shows that 5-HT synthesis and transport in the hindbrain is suppressed by CIT, which induces rnf38 gene expression in the forebrain where 5-HT neurons project. Thus, the expression of rnf38 is negatively regulated by the serotonergic system.
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Alzheimer's disease (AD), the most common cause of dementia in aging people, is found to have a critical link with the deposition of β-amyloid (Aβ) in the brain. The inhibition of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), a key enzyme for Aβ production, is a promising target for AD therapy. In pursuit to find a potent inhibitor of BACE1, we identified galangin, a natural flavonoid, had a significant lowering effect on Aβ levels. ⋯ We further investigated whether epigenetic mechanisms, such as histone acetylation and DNA methylation, were involved in galangin-induced transcriptional regulation of BACE1. Our data show that galangin induces a decrease of acetylated H3 in the BACE1 promoter regions through the up-regulation of endogenous HDAC1-mediated deacetylation, which is independent of DNA methylation status. The above findings suggest a novel mechanism for polyphenols' neuroprotective effect in neurodegeneration and galangin as a potential drug candidate for AD therapy.
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Multiple sclerosis (MS) is thought to result from a combination of genetics and environmental factors. Several lines of evidence indicate that significant prevalence of anxiety and depression-related disorders in MS patients can influence the progression of the disease. Although we and others have already reported the consequences of prenatal maternal immune activation on anxiety and depression, less is known about the interplay between maternal inflammation, MS and gender. ⋯ Interestingly, the severity of the disease was associated with increased anxiety/depressive-like behaviors and elevated corticosterone or TNF-α levels in both sexes. Overall, these data suggest that maternal immune activation with Poly I:C during mid-pregnancy increases anxiety- and depressive-like behaviors, and the clinical symptoms of EAE in a sex-dependent manner in non-EAE or EAE-induced offspring. Finally, the progression of EAE in offspring seems to be linked to maternal immune activation-induced dysregulation in neuro-immune-endocrine system.
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Parkinson's disease (PD) is characterized by selective loss of dopaminergic neurons in the substantia nigra (SN). Epidemiological evidence has suggested a link between type 2 diabetes and PD, although the mechanisms remain largely unknown. We applied LC-MS/MS-based pattern analysis to investigate altered proteomes in the SN of db/db mice (db-SN) and high-fat diet mice (HFD-SN), revealing that the level of mitochondrial proteins has changed in the SN of diabetic mice compared to that of control mice. ⋯ Interestingly, these alterations were reversed by the administration of metformin, one of most frequently prescribed anti-hyperglycemic agents. The slight loss of dopaminergic neurons was found in chronic HFD-SN that was restored by metformin. Taken together, our data suggest that the dysregulation of Parkin-PARIS-PGC-1α pathway by metabolic malregulation may contribute to the pathogenesis of PD and metformin might exert a neuroprotective effect on PD via the restoration of parkin.