Scalp acupuncture improves disordered behavior in the valproic acid-induced rat model of autism

Abstract

Objectives

To investigate the underlying mechanisms of scalp acupuncture treatment (SAT) on autism spectrum disorder (ASD).

Methods

Thirty male Wistar rat pups that had been prenatally exposed to valproic acid sodium (VPA) were randomly divided into the VPA, VPA+acupoint, and VPA+ non-acupoint groups using the random number table method, with 10 rats in each group. Ten pups who had been prenatally exposed to saline were assigned to the control group (CG). There was no intervention in either the control or VPA groups. In the acupoint group, “Shenting (GV24),” bilateral “Benshen (GB13)” were manipulated. In the non-acupoint group, the area below the costal space was stimulated. Acupuncture stimulation lasted for 40 min, with manual twisting of the needles every 10 min, 5 days/week, with 2 days of rest per week, for a total duration of 4 weeks. After the corresponding treatments, behavioral tests (including the open field, social interaction, and Morris water maze tests) were performed to evaluate the therapeutic effects. RT-PCR and Western blotting were performed to detect the expression of neuregulin 1 (NRG1)/ErbB4.

Results

In the open field test, the activity time spent in the central area in the VPA+acupoint group was significantly longer than that in the VPA group and VPA+ non-acupoint group (both P<0.05). The total length in the VPA+acupoint group was significantly longer than that in the VPA group (P<0.05). The number of bouts in the central area of the VPA+acupoint group was significantly higher than that of the VPA group (P<0.05). In session I of social interaction test, all experimental rats spent more time interacting with stranger 1 (all P<0.05). In session II, the CG and VPA+acupoint groups rats showed more interest in searching for new strangers, but the VPA+non-acupoint group spent more time interacting with stranger 1 than with stranger 2(all P<0.05). In the Morris water maze test, compared with the VPA group, the latency of the VPA+acupoint group was shorter (day 2, 3, 4, 5, P<0.05); compared with VPA+acupoint group, the latency of the VPA+non-acupoint group was longer (day 2, 4, P<0.05). The mean distance in the VPA+acupoint group was shorter than that in the VPA group (day 3, 5, P<0.05). The platform quadrant time of the VPA+non-acupoint group was significantly shorter than that of the VPA+acupoint group (P<0.05) (day 6). The VPA+acupoint group had more platform crossings than the VPA group (P<0.05), and the VPA+ non-acupoint group had fewer platform crossings than the VPA+acupoint group (P<0.05) (day 6). After SAT, the expression levels of NRG1 and ErbB4 proteins in the VPA+acupoint group were significantly increased than those in the VPA group (both P<0.05) in the medial prefrontal cortex (mPFC). The expression levels of NRG1 and ErbB4 proteins in VPA+non-acupoint group were significantly less than those in the VPA+acupoint group (both P<0.05) in the mPFC. After SAT, the expression levels of NRG1 and ErbB4 proteins in the VPA+acupoint group were significantly higher than those in the VPA group (both P<0.05) in the hippocampus. The expression levels of NRG1 and ErbB4 proteins in the VPA+non-acupoint group were significantly lower than those in the VPA+acupoint group (both P<0.05) in the hippocampus. After SAT, the expression levels of mRNA levels of NRG1-ErbB4 in the mPFC and hippocampus in VPA+acupoint group were significantly higher than those in the VPA group (all P<0.05). The mRNA expression levels of NRG1-ErbB4 in the mPFC and hippocampus in VPA+ non-acupoint group were significantly lower than those in the VPA+acupoint group (all P<0.05).

Conclusions

Our results suggest that SAT can improve ASD-like behaviors in young rats in a VPA model of ASD. This may be related to its function in upregulating the expression of protein and gene of NRG1 and its receptor ErbB4 in the mPFC.