AbstractAutism is known as a severe neurobehavioral syndrome, with males affected more often than females. Previous studies have revealed that microRNAs (miRNAs) play a critical role in the search for novel therapeutic strategies for autism. Therefore, we evaluate the ability of miR-153 to influence brain-derived neurotrophic factor (BDNF) of autism as well as proliferation and apoptosis of hippocampal neuron through the janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway by targeting leptin receptor (LEPR). Firstly, the autistic mice models were established and Morris water maze was employed for the analysis of the learning ability and memory of the mice. Besides, in vitro experiments were conducted with the transfection of different mimic, inhibitor, or siRNA into the hippocampal neuron cells, after which the effect of miR-153 on LEPR and the JAK-STAT signaling pathway-related factors was investigated. Next, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and flow cytometry assay were conducted to evaluate cell proliferation, cell cycle, and apoptosis respectively following transfection. The results revealed that there was a significant decrease in learning ability and memory in the autistic mice along with a reduction in the positive expression rate of BDNF and serious inflammatory reaction. LEPR was confirmed as a target gene of miR-153 by the dual luciferase reporter gene assay. After transfection of overexpressed miR-153, LEPR and the JAK-STAT signaling pathway were inhibited followed by an increase in BDNF and enhancement of cell proliferation. In conclusion, the high expression of miR-153 can inhibit activation of JAK-STAT signaling pathway by LEPR, thus improving BDNF expression and the proliferative ability of hippocampal neurons.
Xiaoyao powder alleviates the hippocampal neuron damage in chronic unpredictable mild stress-induced depression model rats in hippocampus via connexin 43Cx43/glucocorticoid receptor/brain-derived neurotrophic factor signaling pathway
