Neuroscience
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Rearing rodents in an enriched environment (EE), with increased sensory stimulations and social interactions, is a well-established model for naturally increasing neural activity. It is well-known that EE-rearing of rodents from adolescence or during adulthood leads to extensive biochemical, morphological, electrophysiological and behavioral changes. Here, we examine the effects of EE-rearing from birth on adult behavior. ⋯ Moreover, EE-reared mice showed reduced anxiety in novel environments and enhanced social interactions. Together, these results demonstrated that EE-rearing from birth significantly improved motor ability, learning and memory and sociability, while reducing anxiety. A better understanding of how early environmental influences affect behavior is not only important for understanding neural circuit wiring, but also provides insight into developing more effective intervention programs for neurodevelopmental disorders.
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The basal nucleus of Meynert (BNM) shows structural abnormalities in Parkinson's disease with mild cognitive impairment (PD-MCI). However, it is yet unknown whether functional connectivity (FC) in the BNM (BNM-FC) is altered in patients with PD-MCI. Therefore, in this study, we compared the BNM-FC of patients with PD-MCI and PD patients with normal cognition (PD-NC), to evaluate the relationship between the observed differences of BNM-FC and neuropsychological test scores. ⋯ We found that 86.36% subjects were correctly classified based on the BNM-FC using the leave-one-out cross-validation (LOOCV) method, with a sensitivity of 90.91% and specificity of 81.82%. Our study provides new insights into the neural basis of cognitive dysfunction in PD patients. We also found that BNM-FC can be an effective feature to distinguish PD-MCI from PD-NC.
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Choline acetyltransferase (ChAT) synthesizes the neurotransmitter acetylcholine (Ach). Exogenous supplementation with ChAT can functionally compensate for decreased Ach levels and ameliorate memory and cognitive deficits. In this paper, the treatment efficacy of recombinant ChAT (peptide transduction domain (PTD)-ChAT) and donepezil were compared in aged dementia mice, and their mechanisms were explored by performing the gene function annotation and enrichment analysis of differentially expressed genes. ⋯ Donepezil was significantly correlated with the immune inflammatory response and the insulin and IGF-1 signaling pathways. Therefore, although PTD-ChAT and donepezil were both effective in the treatment of aged dementia mice, their mechanisms were significantly different. Our research indicated that PTD-ChAT has potential promise for research on new drugs for AD treatment.
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The Na+/K+-ATPase is a transmembrane ion pump that has a critical homeostatic role within every mammalian cell; however, it is vulnerable to the effects of increased oxidative stress. Understanding how expression of this transporter is influenced by oxidative stress may yield insight into its role in the pathophysiology of neurological and neuropsychiatric diseases. In this study we investigated whether increased oxidative stress could influence Na+/K+-ATPase expression in various brain regions of mice. ⋯ Despite increased staining for oxidative stress in higher brain, no differences in α1 or α3 expression were noted in Aldh2-/- mice versus wildtype, or in mice exposed to a 28-day chronic unpredictable stress protocol. In both models of oxidative stress, gene and protein expression of Na+/K+-ATPase α1 and α3 isoforms within the higher and lower brain was remarkably stable. Thus, Na+/K+-ATPase function previously reported as altered by oxidative stress is not through induced changes in the expression of pump isoforms.
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Microglia-mediated neuroinflammation plays a significant role in the pathogenesis of Parkinson's disease (PD). Down-regulation of DJ-1, a PD-associated protein, has been recently found to increase microglial sensitivity to lipopolysaccharides (LPS). However, the role of DJ-1 in microglia-mediated neuroinflammation in PD remains unclear. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish a PD model with mice and tyrosine hydroxylase (TH) staining was performed to validate the model. ⋯ Furthermore, DJ-1 regulated the expression of NLRP3 by upregulating Nrf2/Trx1 axis. Taken together, these data suggested that down-regulation of DJ-1 accelerated microglia-mediated neuroinflammation and cell apoptosis via Nrf2/Trx1/NLRP3 axis. Thus, our results demonstrated the important role of DJ-1 in PD pathogenesis and warranted further investigation of DJ-1 as a therapeutic target for PD.