Neuroscience
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Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by decreased learning ability and memory deficits. Our previous findings suggested that benzene, 1,2,4-trimethoxy-5-(2-methyl-1-propen-1-yl) (BTY) can ameliorate the dysfunction of GABAergic inhibitory neurons associated with neurological diseases. On this basis, we investigated the neuroprotective effect of BTY on AD and explored the underlying mechanism. ⋯ Besides, histopathological experiments indicated that BTY could maintain the morphology and function of neurons, reduce amyloid β-protein 42 (Aβ42) and phosphorylated tau (p-tau) accumulation, and decrease the levels of inflammatory cytokines. Finally, western blot experiments showed that BTY could inhibit the expression of apoptosis-related proteins and promote the expression of memory-related proteins. In conclusion, this study indicated that BTY may be a promising drug candidate for AD.
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The nucleus accumbens (NAc) is considered an interface between motivation and action, with NAc neurons playing an important role in promoting reward approach. However, the encoding by NAc neurons that contributes to this role remains unknown. We recorded 62 NAc neurons in male Wistar rats (n = 5) running towards rewarded locations in an 8-arm radial maze. ⋯ Together, these neurons accounted for most of the speed and acceleration encoding identified in our analysis. In contrast, a further 16% of neurons presented a valley during acceleration followed by a peak just prior to or after reaching reward (deceleration-on cells). These findings suggest that these three classes of NAc neurons influence the time course of speed changes during locomotor approach to reward.
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Apolipoprotein E (apoE, protein; APOE, gene), divided into three alleles of E2, E3 and E4 in humans, is associated with the progression of white matter lesion load. However, mechanism evidence has not been reported regarding the APOE genotype in early white matter injury (WMI) under subarachnoid hemorrhage (SAH) conditions. In the present study, we investigated the effects of APOE gene polymorphisms, by constructing microglial APOE3 and APOE4-specific overexpression, on WMI and underlying mechanisms of microglia phagocytosis in a mice model of SAH. ⋯ The increased ROS and aggravating mitochondrial damage demonstrated that the damaging effects of APOE4 in SAH may be associated with microglial oxidative stress-dependent mitochondrial damage. Inhibiting mitochondrial oxidative stress by Mitoquinone (mitoQ) can enhance the phagocytic function of microglia. In conclusion, anti-oxidative stress and phagocytosis protection may serve as promising treatments in the management of SAH.
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The frontoparietal network (FPN) and cingulo-opercular network (CON) may exert top-down regulation corresponding to the central executive system (CES) in working memory (WM); however, contributions and regulatory mechanisms remain unclear. We examined network interaction mechanisms underpinning the CES by depicting CON- and FPN-mediated whole-brain information flow in WM. We used datasets from participants performing verbal and spatial working memory tasks, divided into encoding, maintenance, and probe stages. ⋯ Task-level output was slightly stronger for the CON. CON → FPN, CON → DMN, visual areas → CON, and visual areas → FPN showed consistent effects. The CON and FPN might together underlie the CES's neural basis and achieve top-down regulation through information interaction with other large-scale functional networks, and the CON may be a higher-level regulatory core in WM.
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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease related to the progressive death of motor neurons. Understanding the pathogenesis of ALS continues to provide considerable challenges. Bulbar-onset ALS involves faster functional loss and shorter survival time than spinal cord-onset ALS. ⋯ This miRNA was found to directly target ERBB4 and regulate the AKT/GSK3β pathway. Collectively, the above miRNAs and their targets are related to the development of bulbar-onset ALS. Our research indicates that miR-23a-3p might have an effect on motor neuron loss observed in bulbar-onset ALS and may be a novel target for the therapy of ALS in the future.