Neuroscience
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Enriched environment (EE) is effective in preventing cerebral ischemia-reperfusion (I/R) injury. However, little is known about the mechanism underlying the neuroprotection of EE preprocessing. Endoplasmic reticulum (ER) stress has been demonstrated to be extensively involved in I/R injury. ⋯ Our results showed that pre-ischemic EE inhibited the ER stress, as evidenced by the inactivation of activating transcription factor 6 (ATF6), protein kinase RNA (PKR)-like ER kinase (PERK), and inositol-requiring enzyme 1 (IRE1) pathways. Moreover, the rats reared in EE were detected with lower autophagic activity and apoptosis levels. The decrease in activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), and phospho-c-Jun N-terminal kinases (p-JNK) expression suggested EE pretreatment might inhibit autophagy and apoptosis via modulating ER stress-mediated PERK-ATF4-CHOP and IRE1-JNK signal pathways, which provides a new idea for the prevention of the deleterious cerebral and functional consequences of ischemic stroke.
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Memory impairment is one of the neuropsychological effects of hypobaric hypoxia (HH), which can be associated with programmed cell death, such as apoptosis and ferroptosis. Emerging evidence indicates crosstalk between apoptosis and ferroptosis, while the crosstalk between HH-induced apoptosis and ferroptosis in the hippocampus has not been clarified. Here, microarray profiles were extracted to analyze the differentially expressed genes with and without HH exposure, and keratin 18 (Krt18) was found to be a potential gene related to both apoptosis and ferroptosis. ⋯ Combined with the real-time q-PCR analysis, the mRNA expression of Krt18 decreased significantly after HH exposure for 1 day and 3 days, and Mapk10 (JNK3) was upregulated at the corresponding time points. After exposure for 7 days, Krt18 and JNK3 showed no significant change. In conclusion, Krt18 may regulate apoptosis and ferroptosis simultaneously, possibly via the JNK signaling pathway, which might provide a potential central target for apoptosis and ferroptosis in hippocampal injury after HH exposure.
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Alzheimer's disease (AD) is a chronic neurological disorder with high morbidity. Exercise is one of the effective ways to ameliorate AD. In this study, we assessed the effects of exercise on cognition and inflammation and studied the role of miR-148a-3p in AD. ⋯ MiR-148a-3p silencing reversed these abovementioned tendencies. Patients with AD exhibited a low level of miR-148a-3p, which was increased after exercise. Therefore, exercise might improve the cognitive function and memory of mice with AD by upregulating miR-148a-3p.
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Locomotor movements in mammals are generated by neural networks, situated in the spinal cord, known as central pattern generators (CPGs). Recently, significant strides have been made in the genetic identification of interneuronal components of the locomotor CPG and their specific function. Despite this progress, a population of interneurons that is required for locomotor rhythmogenesis has yet to be identified, and it has been suggested that subsets of interneurons belonging to several genetically-defined populations may be involved. ⋯ Focal application of 5-hydroxytryptamine creatine sulfate complex (5-HT) and N-methyl-D-aspartate (NMDA) to the central canal of the rostral lumbar segments of newborn male and female mouse spinal cords quickly generates a robust pattern of fictive locomotion, while inhibition or ablation of neurons in this region disrupts the locomotor rhythm in both rostral and caudal lumbar segments. When applied to the central canal at caudal lumbar levels a higher volume of 5-HT and NMDA are required to elicit fictive locomotion, while inhibition of neurons surrounding the central canal at caudal levels again interrupts rhythmic activity at local segmental levels with minimal effects rostrally. The results of this study indicate that interneurons in the most medial laminae of the neonatal mouse spinal cord are both necessary and sufficient for the generation of locomotor activity, and suggests that this is the region where the rhythm generating core of the locomotor CPG resides.