Neuroscience
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Aquaporins (AQPs) play critical physiological roles in water balance in the central nervous system (CNS). Aquaporin-4 (AQP4), the principal aquaporin expressed in the CNS, has been implicated in the processing of sensory and pain transmission. Akt signaling is also involved in pain mediation, such as neuroinflammatory pain and bone cancer pain. ⋯ Furthermore, Akt blockade with MK2206 alleviated NP in the early and late phases after SNL. These results elucidate the mechanisms involved in the roles of Akt/AQP4 signaling in the development and maintenance of NP. AQP4 is likely to be a novel therapeutic target for NP management.
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Academic self-concept, which can be defined as one's beliefs about their academic ability, plays an important role in students' future academic achievement. Here, we examined the neuroanatomical substrates underlying academic self-concept in 92 school-aged children (9.90 ± 0.85 years, 41 girls) using voxel-based morphometry of images obtained by structural magnetic resonance imaging. ⋯ Region of interest analyses further showed that regional gray matter volume in the right DLPFC could significantly predict achievement 1 year after assessment. Notably, mediation analyses suggested that regional gray matter volume in the right DLPFC mediated the effect of academic self-concept on students' future academic achievement.
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FK501 binding protein 51 (FKBP5) is a stress response prolyl isomerase that inhibits the translocation of the glucocorticoid receptor (GR) heterocomplex to the nucleus. Previous studies have shown that the expression levels of FKBP5 are positively correlated with psychiatric disorders, including depression and post-traumatic stress disorder. In rodents, FKBP5 deletion in the brain leads to be resilient to stress-induced depression. ⋯ In the hippocampus, GR activation alters the release probability in inhibitory synapses as well as the postsynaptic contribution of glutamate receptors in excitatory synapses; however, no such alterations were induced in the absence of FKBP5. FKBP5 deficiency causes insensitivity to activated GRs in the hippocampus suggesting that FKBP5 mediates synaptic changes caused by GR activation. Our study provides electrophysiological evidence of stress resilience observed in FKBP5-deficient mice.
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Neonatal hypoxic-ischemic brain damage (HIBD) is one of the main causes of neonatal acute death and chronic nervous system impairment, but still lacks effective treatments. ZNF580/ZFP580, reported in our previous studies, may be a newly identified member of the Krüppel-like factor (KLF) family, and has anti-apoptotic effects during ischemic myocardial injury. In the present study, we showed that the expression levels of both ZFP580/ZNF580 mRNA and protein increased significantly in neonatal HIBD rats and oxygen-glucose deprivation (OGD) SH-SY5Y cell models. ⋯ Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that these DEGs were found in some pathways, including ferroptosis, glutamatergic synapses, protein processing in the endoplasmic reticulum, estrogen signaling pathways, the TGF-beta signaling pathway, and the longevity regulating pathway. The qRT-PCR validation results were consistent with RNA-seq results, which showed that HSPA5, IGFBP3, NTN4, and KLF9 increased in ZNF580-overexpressed SH-SY5Y cells and decreased in interference-expressed SH-SY5Y cells, when compared with normal cells. Together, the results suggested that ZNF580 targeted these genes to inhibit neuronal apoptosis.
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The cerebellum has been shown to be involved in temporal information processing. We recently demonstrated that neurons in the cerebellar dentate nucleus exhibited periodic activity predicting stimulus timing when monkeys attempted to detect a single omission of isochronous repetitive visual stimulus. In this study, we assessed the relative contribution of signals from Purkinje cells and mossy and climbing fibers to the periodic activity by comparing single neuronal firing before and during local infusion of GABA or glutamate receptor antagonists (gabazine or a mixture of 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide hydrate (NBQX) and (±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP)). ⋯ We also found that the variation of baseline activity decreased during gabazine application but sometimes increased during the blockade of glutamate receptors. These changes were not observed during prolonged recording without drug administration. These results suggest that the predictive neuronal activity in the dentate nucleus may mainly attribute to the inputs from the cerebellar cortex, while the signals from both mossy fibers and Purkinje cells may play a role in setting the level and variance of baseline activity during the task.