Neuroscience
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Thioredoxin system plays an important role in maintaining the cellular redox balance. Recent evidence suggests that thioredoxin (Trx) system may promote cell survival and neuroprotection. In this study, we explored the role of thioredoxin system in neuronal differentiation using a primary mouse cortical neuronal cell culture. ⋯ However, treatment with CB3, a Trx-mimetic tripeptide, rescued H2O2-decreased CREB phosphorylation. Our results suggest that Trx regulates neuronal differentiation and maturation of primary mouse cortical neurons by targeting CREB neurotrophic pathway. Trx may regulate CREB activation by maintaining the cellular redox balance.
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The endocannabinoid (eCB) system plays an important role in regulating the stress response, including glucocorticoid release and the generation of avoidance behaviour. Its two major ligands, 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (anandamide; AEA), are dynamically influenced by psychological stress to gate the generation of the stress response and facilitate recovery upon stress termination. Many biological systems exhibit circadian "daily" rhythms, including glucocorticoids and endocannabinoids, and the behavioural and endocrine impact of stress is modulated by the time of day. ⋯ We found that overall, stress decreased AEA in the AMY and HIP, with an effect in the PFC dependent on the time of day. Conversely, stress increased 2-AG in the AMY, with an effect in the PFC and HIP dependent on the time of day. This suggests that stress has a similar overall impact on eCB levels regardless of circadian phase, but that subtle differences may occur depending on the brain region, especially the PFC.
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Cerebral ischemia (CI) is the main cause of stroke morbidity and disability. This study aims to identify the early molecular regulation responsible for the therapeutic effectiveness of the Herb pair Danshen-Honghua (DH) for CI. The major targets of DH were identified by searching the public database of traditional Chinese medicine (TCM). ⋯ These genes were primarily enriched in biological processes including wound healing, reaction to oxidative stress, and response to peptides, lipid and atherosclerosis, Age-rage signaling pathway, and TNF signaling pathway by KEGG and GO enrichments. The effective components of DH had stable binding to these key targets by molecular docking. Finally, it was verified that the mechanism of DH on CI treatment may be related to the activation of the TNF-α/JNK signaling pathway by establishing the middle cerebral artery occlusion (MCAO) rat model.
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In both people and animals, exposure to adverse experiences early in life can alter neurodevelopment and lead to long-term behavioral effects, including effects on reward processing. In the current study, we use a well-validated rodent model of maternal neglect, maternal separation (MS), to investigate the impact of early life adversity on reward learning and motivation and identify associated modifications in cellular activation in reward-relevant areas. Litters of Long-Evans rats were separated from the dam for either 15 min (brief) or 180 min (prolonged)/day from postnatal day (PND)2 to PND14. ⋯ MS180-induced changes in c-Fos expression in the dorsal and ventral striatum were observed, with subregion-specific effects along the rostrocaudal axis. Moreover, regression analyses suggest that motivated responding for a sucrose food reward in MS180-exposed, but not MS15-exposed animals, was associated with increased c-Fos expression in the rostral nucleus accumbens core. These findings implicate specific striatal regions in sex-specific modulation of sustained effort-based reward behavior following early life adversity.
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Rett syndrome (RTT) is a debilitating neurodevelopmental disorder caused by mutations in the X-linked methyl-CpG-binding protein 2 (MeCP2) gene, resulting in severe deficits in learning and memory. Alterations in synaptic plasticity have been reported in RTT, however most electrophysiological studies have been performed in male mice only, despite the fact that RTT is primarily found in females. In addition, most studies have focused on excitation, despite the emerging evidence for the important role of inhibition in learning and memory. ⋯ This failure to induce LTP was accompanied by excitation/inhibition (E/I) imbalances and altered excitability, in a sex- and cell-type specific manner. Specifically, NGF interneurons of male RTT mice displayed increased intrinsic excitability, a depolarized resting membrane potential, and decreased E/I balance, while in female RTT mice, the resting membrane potential was depolarized. Understanding the role of NGF interneurons in RTT animal models is crucial for developing targeted treatments to improve cognition in individuals with this disorder.