Abstract
Autism 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.
Highlights
Autism, a kind of life-long neurodevelopmental disability, is often accompanied with people’s deficiencies in social interaction, communication, and repeated and stereotyped behaviors [1]
Compared with the normal saline (NS) group, the VPA group exhibited significantly increased positive expression rate of leptin receptor (LEPR) and decreased expression rate of brain-derived neurotrophic factor (BDNF) (P < 0.05) (Figure 1B). These findings suggested that autistic mice had decreased BDNF expression and increased LEPR increases
Enzyme-linked immunoassay (ELISA) was performed in order to investigate the inflammatory factor levels, and the results in Table 4 showed that compared with the NS group, the VPA group significantly increased the expression of IL-6, IL-1β, and tumor necrosis factor alpha (TNF-α) in the serum (P < 0.05)
Summary
A kind of life-long neurodevelopmental disability, is often accompanied with people’s deficiencies in social interaction, communication, and repeated and stereotyped behaviors [1]. MiR-153, an intronic miRNA recognized as a modulator of alpha-synuclein at post-transcription level, has been identified to be a significant component of the brain with an example that reflects synuclein expression in different tissues in the period of neuronal development, indicating that they take coordinated effects in alpha-synuclein [14]. With the utilization of janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibitors, the JAK-STAT signaling pathway regulates the innate immune response and improves neuroinflammation, which is essential for the development and function of both innate and adaptive immunity [19]. There’s been an increase in research demonstrating the role of miRNA in autism pathogenesis; there is lack of information regarding the correlation between miR-153 and autism. The present study was conducted to explore the effect of miR-153 alternations on autism involving the JAK-STAT signaling pathway
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