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. 2023 Apr 18:19:951-972.
doi: 10.2147/NDT.S398321. eCollection 2023.

Acupuncture Ameliorated Behavioral Abnormalities in the Autism Rat Model via Pathways for Hippocampal Serotonin

Sijie Chen #  1 , Longsheng Huang #  2 , Guihua Liu  2 , Jie Kang  3 , Qinfang Qian  2 , Jingrong Wang  4 , Rong Wang  1 , Lizhen Zheng  1 , Haijun Wang  5 , Ping Ou  2
Affiliations

Acupuncture Ameliorated Behavioral Abnormalities in the Autism Rat Model via Pathways for Hippocampal Serotonin

Sijie Chen et al. Neuropsychiatr Dis Treat. .

Abstract

Purpose: Acupuncture can improve symptoms of autism spectrum disorder (ASD), but the potential mechanisms remain undefined. So, we aimed to explore the behavioral improvement of autism rat model after acupuncture and to describe the potential molecular mechanism underlying these changes.

Patients and methods: Wistar rats were intraperitoneally injected with VPA 12.5 days after conception, and their offspring were considered as good models of autism. Experimental rats were divided into three groups (wild-type (WT), n = 10; VPA, n = 10; and VPA_acupuncture, n = 10). VPA_acupuncture group rat received 4 weeks of acupuncture treatment (Shéntíng (GV24), and Bilateral Běnshén (GB13)) on the 23rd day after birth. All rats were subjected to behavioral tests, including social interaction, open field, and Morris water maze tests. Afterwards, hippocampal tissues (left side) were removed and subjected to RNA sequencing (RNA-seq) analysis; ELISA was also used to detect the associated serotonin levels in the hippocampus.

Results: Behavioral tests showed that acupuncture treatment improved spontaneous activity, aberrant social interaction, and alleviated impaired learning and memory in the VPA-induced rat model. Differentially expressed genes (DGEs) analysis showed 142 significantly differentially expressed genes between WT and VPA groups, and 282 between VPA and VPA_acupuncture rats. Htr2c and Htr1a, 5-HT receptor genes, were up-regulated in the VPA group compared with WT group. Additionally, Tph1, a rate-limiting enzyme gene of 5-HT synthesis, was up-regulated after acupuncture. These genes were confirmed to have the same trend of expression obtained by RT-qPCR and RNA seq. Furthermore, the concentration of serotonin in the hippocampus in the VPA group was significantly lower than the WT and VPA_acupuncture groups.

Conclusion: Acupuncture improved abnormal behavioral symptoms in the VPA-induced rat model. Further experiments showed that the improvement of the serotonin system may be one of the main regulatory mechanisms of acupuncture for treating ASD.

Keywords: RNA-sequencing; acupuncture; autism; behavioral abnormalities.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Experimental diagram of acupuncture and behavior tests.
Figure 2
Figure 2
Results of open field test.
Figure 3
Figure 3
Results of social interactions test.
Figure 4
Figure 4
Results of MWM test.
Figure 5
Figure 5
Genes differentially expressed among 3 groups of experimental rats.
Figure 6
Figure 6
Genes differentially expressed between the two groups.
Figure 7
Figure 7
GO enrichment analysis of differentially expressed genes between WT and VPA group.
Figure 8
Figure 8
GO enrichment analysis of differentially expressed genes between VPA and VPA_acupuncture group.
Figure 9
Figure 9
KEGG enrichment analysis of differentially expressed genes between WT and VPA group.
Figure 10
Figure 10
KEGG enrichment analysis of differentially expressed genes between VPA and VPA_acupuncture group.
Figure 11
Figure 11
Results of cluster analysis (WT group vs VPA group).
Figure 12
Figure 12
Results of cluster analysis (VPA group vs VPA_acupuncture group).
Figure 13
Figure 13
The results of RT-qPCR.
Figure 14
Figure 14
Determination of serotonin level in hippocampus of three group rats.
See this image and copyright information in PMC

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