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MicroRNA-153 promotes brain-derived neurotrophic factor and hippocampal neuron proliferation to alleviate autism symptoms through inhibition of JAK-STAT pathway by LEPR

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-d...

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Autores principales: You, Yu-Hui, Qin, Zhi-Qiang, Zhang, Huan-Li, Yuan, Zhao-Hong, Yu, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591574/
https://www.ncbi.nlm.nih.gov/pubmed/30975733
http://dx.doi.org/10.1042/BSR20181904
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author You, Yu-Hui
Qin, Zhi-Qiang
Zhang, Huan-Li
Yuan, Zhao-Hong
Yu, Xin
author_facet You, Yu-Hui
Qin, Zhi-Qiang
Zhang, Huan-Li
Yuan, Zhao-Hong
Yu, Xin
author_sort You, Yu-Hui
collection PubMed
description 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.
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spelling pubmed-65915742019-06-27 MicroRNA-153 promotes brain-derived neurotrophic factor and hippocampal neuron proliferation to alleviate autism symptoms through inhibition of JAK-STAT pathway by LEPR You, Yu-Hui Qin, Zhi-Qiang Zhang, Huan-Li Yuan, Zhao-Hong Yu, Xin Biosci Rep Research Articles 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. Portland Press Ltd. 2019-06-25 /pmc/articles/PMC6591574/ /pubmed/30975733 http://dx.doi.org/10.1042/BSR20181904 Text en © 2019 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
You, Yu-Hui
Qin, Zhi-Qiang
Zhang, Huan-Li
Yuan, Zhao-Hong
Yu, Xin
MicroRNA-153 promotes brain-derived neurotrophic factor and hippocampal neuron proliferation to alleviate autism symptoms through inhibition of JAK-STAT pathway by LEPR
title MicroRNA-153 promotes brain-derived neurotrophic factor and hippocampal neuron proliferation to alleviate autism symptoms through inhibition of JAK-STAT pathway by LEPR
title_full MicroRNA-153 promotes brain-derived neurotrophic factor and hippocampal neuron proliferation to alleviate autism symptoms through inhibition of JAK-STAT pathway by LEPR
title_fullStr MicroRNA-153 promotes brain-derived neurotrophic factor and hippocampal neuron proliferation to alleviate autism symptoms through inhibition of JAK-STAT pathway by LEPR
title_full_unstemmed MicroRNA-153 promotes brain-derived neurotrophic factor and hippocampal neuron proliferation to alleviate autism symptoms through inhibition of JAK-STAT pathway by LEPR
title_short MicroRNA-153 promotes brain-derived neurotrophic factor and hippocampal neuron proliferation to alleviate autism symptoms through inhibition of JAK-STAT pathway by LEPR
title_sort microrna-153 promotes brain-derived neurotrophic factor and hippocampal neuron proliferation to alleviate autism symptoms through inhibition of jak-stat pathway by lepr
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591574/
https://www.ncbi.nlm.nih.gov/pubmed/30975733
http://dx.doi.org/10.1042/BSR20181904
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