Neuroscience
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Alzheimer's disease (AD) is a debilitating neurodegenerative disease, characterized by extracellular deposition of senile plaques, mostly amyloid β-protein (Aβ) and neuronal loss. The neuroprotective effects of erythropoietin (EPO) have been reported in some models of neurodegenerative disease, but because of its hematopoietic side effects, its derivatives lacking hematopoietic bioactivity is recommended. In this study, the neuroprotective effects of carbamylated erythropoietin-Fc (CEPO-Fc) against beta amyloid-induced memory deficit were evaluated. ⋯ CEPO-Fc treatment prevented the elevation of hippocampal of P38, ERK, MMP-2 activity and also Akt/GSK-3β signaling impairment induced by Aβ25-35 but it had no effect on JNK. It seems that CEPO-Fc prevents Aβ-induced learning and memory deterioration, and also modulates hippocampal MAPKs, Akt/GSK-3β and MMP-2 activity. This study suggests that CEPO-Fc can be considered as a potential therapeutic strategy for memory deficits like AD.
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Neuronal apoptosis plays important roles in the early brain injury after subarachnoid hemorrhage (SAH). This study first showed that inhibition of activating transcription factor 6 (ATF6) by apelin-13 could reduce endoplasmic reticulum (ER)-stress-mediated apoptosis and blood-brain-barrier (BBB) disruption after SAH. We chose apelin-13, ATF6 and CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) siRNAs to verify the hypothesis. ⋯ What's more, the administration of apelin-13 could reduce brain edema, ameliorate BBB disruption and improve neurological functions. However, the CHOP siRNA could significantly reverse the pro-apoptotic effect induced by the increased ATF6 level after SAH. Apelin-13 could exert its neuroprotective effects via suppression of ATF6/CHOP arm of ER-stress-response pathway in the early brain injury after SAH.
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For Parkinson's disease (PD), the regulatory mechanism of α-synuclein (α-syn) aggregation remains to be clarified. Ubiquitination modification is crucial for α-syn aggregation, with implications for Lewy body formation. Besides, ubiquitin ligase absentia homolog (siAH) is involved in the ubiquitination of α-syn. ⋯ In cellular models of rotenone-mediated neurotoxicity, the interactions between p75 and siAH were revealed by immunoprecipitation; the colocalization of p75 with α-syn was observed in the cytoplasm; p75 promoted nuclear expression of NF-κB (p65), which might interact with the promoter of the siAH gene. Moreover, siRNA-mediated p75 depletion reduced the upregulation of α-syn and nuclear expression of p65 and protected against cell apoptosis induced by rotenone. Thus, aberrant expression of p75 may regulate the increased expression of α-syn, which is related to siAH-mediated ubiquitination and nuclear expression of p65.
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Prenatal exposure to high-fat diet (HFD) might predispose offspring to develop metabolic and mental disorders later in life. Insight into the molecular and behavioral consequences of maternal HFD on offspring is sparse but may involve both neuroinflammation and a dysregulated neuroendocrine stress axis. Thus, the aim of this work was to: (i) investigate the influence of maternal HFD on memory, anxiety and depression-like behavior in adult offspring and (ii) identify possible biological biomarkers related to neuroinflammation and stress responses. ⋯ This behavioral alteration was accompanied by significantly higher mRNA levels of the hippocampal pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) mRNA and monocyte-chemoattractant protein-1 (MCP-1), both of which correlated with degree of behavioral change. Maternal exposure to HFD increased the offspring's levels of hippocampal, corticosteroid releasing hormone receptor 2 (CRHR2) and kynurenine mono oxygenase (KMO) mRNA, whereas kynurenine aminotransferase I (KAT1) mRNA levels were decreased. The present results suggest that neuroinflammatory and stress axis pathways in the hippocampus may contribute to anxiogenic effects of maternal HFD in offspring.
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The purpose of this study was to determine the response, in rat, to chronic physical activity in small and large DRG neurons. Rats were cage-confined or underwent 16-18 weeks of daily increased activity, via 2 h of treadmill running per day or free access to voluntary exercise wheels, following which small (≤30 µm) and large (≥40 µm) diameter DRG neurons were harvested by laser capture microdissection from flash-frozen lumbar DRGs. Relative mRNA levels were determined using real-time polymerase chain reaction. ⋯ In large DRG neurons, voluntary wheel exercise decreased the expression for 5HT1D receptors, whereas both treadmill and voluntary wheel exercise decreased the expression of mRNA for TrkC receptors. DRG neurons show slightly more changes in gene expression after voluntary exercise compared to the treadmill exercise group. Small and large lumbar sensory neurons are responsive to chronically increased neuromuscular activity by changing the expression of genes, the products of which could potentially change the sensory processing of nociceptors and proprioceptors, which could in turn alter functions such as pain transmission and locomotor coordination.