Neuroscience
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with no effective method for its treatment so far. The pathogenesis of AD has been reported, but the endogenous metabolic profile and disease-related biomarkers are still not clear. To better understand AD, an AD model induced by injecting β-amyloid 25-35 (Aβ 25-35) solution into bilateral hippocampus was developed on Sprague-Dawley rats. ⋯ The results showed that compared with healthy control rats, AD rats suffered from cognitive dysfunction, hippocampus damage, Aβ formation and tau phosphorylation at 8 weeks after surgery, suggesting that the Aβ25-35-induced AD model was successfully established. In addition, the levels of γ-aminobutyric acid, acetylcholine, glycine, norepinephrine, serotonin, taurine and dopamine decreased and glutamate and aspartic acid increased in hippocampal tissue of AD rats. 45 altered metabolites mainly involved in 8 metabolic pathways were identified as the endogenous biomarkers of AD. According to the analysis of the biological significance of metabolic profiles, the pathogenesis of AD was mainly due to gut microbiome dysbiosis, inhibition of energy metabolism, oxidative stress injury and loss of neuronal protective substances.
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Previously we described similarities and differences in the organization and molecular composition of an aggrecan based extracellular matrix (ECM) in three precerebellar nuclei, the inferior olive, the prepositus hypoglossi nucleus and the red nucleus of the rat associated with their specific cytoarchitecture, connection and function in the vestibular system. The aim of present study is to map the ECM pattern in a mesencephalic precerebellar nucleus, the pararubral area, which has a unique function among the precerebellar nuclei with its retinal connection and involvement in the circadian rhythm regulation. ⋯ Characteristic perineuronal nets (PNNs) were only recognizable with Wisteria floribunda agglutinin (WFA) and aggrecan staining around some of the medium-sized neurons, whereas the small cells were rarely surrounded by a weakly stained PNNs. The moderate expression of key molecules of PNN, the hyaluronan (HA) and HAPLN1 suggests that the lesser stability of ECM assembly around the pararubral neurons may allow quicker response to the modified neuronal activity and contributes to the high level of plasticity in the vestibular system.
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Transient receptor potential vanilloid type 4 (TRPV4) channels are involved in astrocyte volume regulation; however, only limited data exist about its mechanism in astrocytes in situ. We performed middle cerebral artery occlusion in adult mice, where we found twice larger edema 1 day after the insult in trpv4-/- mice compared to the controls, which was quantified using magnetic resonance imaging. This result suggests disrupted volume regulation in the brain cells in trpv4-/- mice leading to increased edema formation. ⋯ In contrast to in vitro experiments, we found little evidence of the contribution of TRPV4 channels to volume regulation in astrocytes in situ in adult mice. Moreover, we only found a rare expression of TRPV4 channels in adult mouse astrocytes. Our data suggest that TRPV4 channels are not involved in astrocyte volume regulation in situ; however, they play a protective role during the ischemia-induced brain edema formation.
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Emerging evidence suggests that hypoxia-inducible factors (specifically, HIF-1α) and Notch signaling are involved in epileptogenesis and that cross-coupling exists between HIF-1α and Notch signaling in other diseases, including tumors and ischemia. However, the exact molecular mechanisms by which HIF-1α and Notch signaling affect the development of epilepsy, especially regarding neurogenesis, remain unclear. ⋯ The immunoprecipitation data illustrated that HIF-1α activated Notch signaling by physically interacting with the Notch intracellular domain (NICD) in epilepsy. In conclusion, our results suggested that HIF-1α-Notch signaling enhanced neurogenesis in acute epilepsy and that neurogenesis during epileptogenesis was reduced once this pathway was blocked; thus, members of this pathway might be potential therapeutic targets for epilepsy.
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Little is known about the functional relationship between endoplasmic reticulum (ER) stress and development of pain hypersensitivity after nerve injury. The aim of this study was to investigate the role of ER stress in the development of pain hypersensitivity in the dorsal root ganglion (DRG) after spinal nerve ligation (SNL). SNL was performed in male Sprague-Dawley rats. ⋯ Treatment with salubrinal inhibited CHOP expression in L5 DRG and alleviated pain hypersensitivity for 5 days after SNL. Tunicamycin induced ER stress in the DRG and pain hypersensitivity 2 h after treatment. These results demonstrated that ER stress is induced in the injured DRG and contributes to the development of pain hypersensitivity after nerve injury.