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

Authors Zhang J, Liu LM, Ni J

Received 19 October 2016

Accepted for publication 25 November 2016

Published 20 March 2017 Volume 2017:13 Pages 835—842

DOI https://doi.org/10.2147/NDT.S125088

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Prof. Dr. Roumen Kirov

Peer reviewer comments 2

Editor who approved publication: Professor Wai Kwong Tang


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
 

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