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可挽救自闭症模型 BTBR T Itpr3/J 小鼠的自闭症样行为。

rescues autistic‑like behaviours in the BTBR T Itpr3/J mouse model of autism.

机构信息

Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.

Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151‑742, Republic of Korea.

出版信息

Mol Med Rep. 2021 Jun;23(6). doi: 10.3892/mmr.2021.12087. Epub 2021 Apr 21.

DOI:10.3892/mmr.2021.12087
PMID:33880583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8060795/
Abstract

(HJ) is a traditional herbal medicine that exhibits anti‑inflammatory, antimicrobial and anti‑tumor effects that is used for the treatment of hypertension, pulmonary disease and leprosy. Recently, it has also been reported that HJ demonstrates neuroprotective properties in animal models of neurodegenerative diseases. The current study hypothesised that the administration of HJ would exhibit therapeutic effects in autism spectrum disorder (ASD), a neurodevelopmental disorder with lifelong consequences. The BTBR T Itpr3tf/J mouse model of ASD was used to investigate the anti‑autistic like behavioural effects of HJ. Chronic oral administration of the ethanolic extract of HJ significantly increased social interaction, attenuated repetitive grooming behaviour and improved novel‑object recognition in BTBR mice. Anti‑inflammatory effects of HJ in the brain were analysed using immunohistochemistry and reverse‑transcription quantitative PCR analysis. Microglia activation was markedly decreased in the striatum and hippocampus, and pro‑inflammatory cytokines, including C‑C Motif Chemokine Ligand 2, interleukin (IL)‑1β and IL‑6, were significantly reduced in the hippocampus following HJ treatment. Moreover, HJ treatment normalised the phosphorylation levels of: N‑methyl‑D‑aspartate receptor subtype 2B and calcium/calmodulin‑dependent protein kinase type II subunit α in the hippocampus of BTBR mice. The results of the present study demonstrated that the administration of HJ may have beneficial potential for ameliorating behavioural deficits and neuroinflammation in ASD.

摘要

(HJ)是一种传统的草药,具有抗炎、抗菌和抗肿瘤作用,用于治疗高血压、肺病和麻风病。最近,据报道 HJ 在神经退行性疾病的动物模型中还具有神经保护作用。本研究假设 HJ 对自闭症谱系障碍(ASD)具有治疗作用,ASD 是一种具有终身后果的神经发育障碍。本研究采用 BTBR T Itpr3tf/J 自闭症模型小鼠来研究 HJ 的抗自闭症样行为作用。HJ 的慢性口服给予显著增加了社会互动,减轻了重复梳理行为,并改善了 BTBR 小鼠的新物体识别。通过免疫组织化学和逆转录定量 PCR 分析研究了 HJ 在大脑中的抗炎作用。HJ 处理后,纹状体和海马中的小胶质细胞活化明显减少,海马中的促炎细胞因子,包括 C 型趋化因子配体 2、白细胞介素(IL)-1β 和 IL-6,显著减少。此外,HJ 处理还使 BTBR 小鼠海马中 N-甲基-D-天冬氨酸受体亚基 2B 和钙/钙调蛋白依赖性蛋白激酶 II 亚基 α 的磷酸化水平正常化。本研究结果表明,HJ 的给予可能对改善 ASD 中的行为缺陷和神经炎症具有有益的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2793/8060795/4b9dbe3b55b9/mmr-23-06-12087-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2793/8060795/1403515a9459/mmr-23-06-12087-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2793/8060795/39b61a5fe58f/mmr-23-06-12087-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2793/8060795/f85d941cb69e/mmr-23-06-12087-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2793/8060795/dd5f4b265cbf/mmr-23-06-12087-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2793/8060795/b465deb53972/mmr-23-06-12087-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2793/8060795/4b9dbe3b55b9/mmr-23-06-12087-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2793/8060795/1403515a9459/mmr-23-06-12087-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2793/8060795/39b61a5fe58f/mmr-23-06-12087-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2793/8060795/f85d941cb69e/mmr-23-06-12087-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2793/8060795/dd5f4b265cbf/mmr-23-06-12087-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2793/8060795/b465deb53972/mmr-23-06-12087-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2793/8060795/4b9dbe3b55b9/mmr-23-06-12087-g05.jpg

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