Rapamycin modulated brain-derived neurotrophic factor and B-cell lymphoma 2 to mitigate autism spectrum disorder in rats

Jie Zhang,1 Li-Ming Liu,1 Jin-Feng Ni2 1Department of Child Healthcare, 2Department of Pediatrics, Maternal and Children Hospital of Tangshan City, Tangshan, Hebei, People’s Republic of China Abstract: The number of children suffered from autism spectrum disorder (ASD) is increasing dram...

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Autores principales:	Zhang J, Liu LM, Ni J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Autism Spectrum Disorder B-cell lymphoma 2 Brain-derived neurotrophic factor Hippocampus Rapamycin Valproic acid. Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/a01fba71a98549ca89cf4c37d12733f7
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spelling	oai:doaj.org-article:a01fba71a98549ca89cf4c37d12733f72021-12-02T00:22:19ZRapamycin modulated brain-derived neurotrophic factor and B-cell lymphoma 2 to mitigate autism spectrum disorder in rats1178-2021https://doaj.org/article/a01fba71a98549ca89cf4c37d12733f72017-03-01T00:00:00Zhttps://www.dovepress.com/rapamycin-modulated-brain-derived-neurotrophic-factor-and-b-cell-lymph-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Jie Zhang,1 Li-Ming Liu,1 Jin-Feng Ni2 1Department of Child Healthcare, 2Department of Pediatrics, Maternal and Children Hospital of Tangshan City, Tangshan, Hebei, People’s Republic of China Abstract: The number of children suffered from autism spectrum disorder (ASD) is increasing dramatically. However, the etiology of ASD is not well known. This study employed mammalian target of rapamycin inhibitor rapamycin to explore its effect on ASD and provided new therapeutic strategies for ASD. ASD rat model was constructed and valproic acid (VPA) was injected intraperitoneally into rats on pregnancy day 12.5. Offspring from VPA group were divided into ASD group and ASD + rapamycin (ASD + RAPA) group. Compared with normal group, the frequency and duration of social behavior and straight times of ASD group were shortened, but the grooming times were extended. Meanwhile, in ASD group, the average escape latency and the frequency of crossing plates were decreased, the apoptotic index (AI) detected by TUNEL assay was increased, and the expression of brain-derived neurotrophic factor (BDNF) and B-cell lymphoma 2 (Bcl-2) analyzed was decreased with great difference compared with normal group (P<0.01). However, rapamycin treatment in ASD rats mitigated the ASD-like social behavior, such as the frequencies of straight and grooming. Furthermore, rapamycin shortened the average escape latency, but increased the frequency of crossing plates of ASD rats. In hippocampus, rapamycin decreased the AI, but increased the levels of BDNF and Bcl-2 (P<0.01) of ASD rats. These findings revealed that rapamycin significantly mitigated the social behavior by enhancing the expression of BDNF and Bcl-2 to suppress the hippocampus apoptosis in VPA-induced ASD rats. Keywords: autism spectrum disorder, B-cell lymphoma 2, brain-derived neurotrophic factor, hippocampus, rapamycin, valproic acid Zhang JLiu LMNi JDove Medical PressarticleAutism Spectrum DisorderB-cell lymphoma 2Brain-derived neurotrophic factorHippocampusRapamycinValproic acid.Neurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 13, Pp 835-842 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Autism Spectrum Disorder B-cell lymphoma 2 Brain-derived neurotrophic factor Hippocampus Rapamycin Valproic acid. Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Autism Spectrum Disorder B-cell lymphoma 2 Brain-derived neurotrophic factor Hippocampus Rapamycin Valproic acid. Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Zhang J Liu LM Ni J Rapamycin modulated brain-derived neurotrophic factor and B-cell lymphoma 2 to mitigate autism spectrum disorder in rats
description	Jie Zhang,1 Li-Ming Liu,1 Jin-Feng Ni2 1Department of Child Healthcare, 2Department of Pediatrics, Maternal and Children Hospital of Tangshan City, Tangshan, Hebei, People’s Republic of China Abstract: The number of children suffered from autism spectrum disorder (ASD) is increasing dramatically. However, the etiology of ASD is not well known. This study employed mammalian target of rapamycin inhibitor rapamycin to explore its effect on ASD and provided new therapeutic strategies for ASD. ASD rat model was constructed and valproic acid (VPA) was injected intraperitoneally into rats on pregnancy day 12.5. Offspring from VPA group were divided into ASD group and ASD + rapamycin (ASD + RAPA) group. Compared with normal group, the frequency and duration of social behavior and straight times of ASD group were shortened, but the grooming times were extended. Meanwhile, in ASD group, the average escape latency and the frequency of crossing plates were decreased, the apoptotic index (AI) detected by TUNEL assay was increased, and the expression of brain-derived neurotrophic factor (BDNF) and B-cell lymphoma 2 (Bcl-2) analyzed was decreased with great difference compared with normal group (P<0.01). However, rapamycin treatment in ASD rats mitigated the ASD-like social behavior, such as the frequencies of straight and grooming. Furthermore, rapamycin shortened the average escape latency, but increased the frequency of crossing plates of ASD rats. In hippocampus, rapamycin decreased the AI, but increased the levels of BDNF and Bcl-2 (P<0.01) of ASD rats. These findings revealed that rapamycin significantly mitigated the social behavior by enhancing the expression of BDNF and Bcl-2 to suppress the hippocampus apoptosis in VPA-induced ASD rats. Keywords: autism spectrum disorder, B-cell lymphoma 2, brain-derived neurotrophic factor, hippocampus, rapamycin, valproic acid
format	article
author	Zhang J Liu LM Ni J
author_facet	Zhang J Liu LM Ni J
author_sort	Zhang J
title	Rapamycin modulated brain-derived neurotrophic factor and B-cell lymphoma 2 to mitigate autism spectrum disorder in rats
title_short	Rapamycin modulated brain-derived neurotrophic factor and B-cell lymphoma 2 to mitigate autism spectrum disorder in rats
title_full	Rapamycin modulated brain-derived neurotrophic factor and B-cell lymphoma 2 to mitigate autism spectrum disorder in rats
title_fullStr	Rapamycin modulated brain-derived neurotrophic factor and B-cell lymphoma 2 to mitigate autism spectrum disorder in rats
title_full_unstemmed	Rapamycin modulated brain-derived neurotrophic factor and B-cell lymphoma 2 to mitigate autism spectrum disorder in rats
title_sort	rapamycin modulated brain-derived neurotrophic factor and b-cell lymphoma 2 to mitigate autism spectrum disorder in rats
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/a01fba71a98549ca89cf4c37d12733f7
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Rapamycin modulated brain-derived neurotrophic factor and B-cell lymphoma 2 to mitigate autism spectrum disorder in rats

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