Transcutaneous auricular vagus nerve stimulation improves social deficits through the inhibition of IL-17a signaling in a mouse model of autism

Wenjing Zhang; Zhiwei Mou; Qi Zhong; Xiaocao Liu; Lan Yan; Lei Gou; Zhuoming Chen; Kwok-Fai So; Li Zhang

doi:10.3389/fpsyt.2024.1393549

Transcutaneous auricular vagus nerve stimulation improves social deficits through the inhibition of IL-17a signaling in a mouse model of autism

Front Psychiatry. 2024 Jun 27:15:1393549. doi: 10.3389/fpsyt.2024.1393549. eCollection 2024.

Authors

Wenjing Zhang^#¹, Zhiwei Mou^#^{1

2}, Qi Zhong^#¹, Xiaocao Liu³, Lan Yan⁴, Lei Gou², Zhuoming Chen¹, Kwok-Fai So⁴, Li Zhang⁴

Affiliations

¹ Department of Rehabilitation Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, China.
² Department of Rehabilitation Medicine, The Fifth Affiliated Hospital of Jinan University, Heyuan, China.
³ Lab of Regenerative Medicine in Sports Science, School of Physical Education and Sports Science, South China Normal University, Guangzhou, China.
⁴ Key Laboratory of Central Nervous System (CNS) Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of Central Nervous System (CNS) Regeneration, Jinan University, Guangzhou, China.

^# Contributed equally.

Abstract

Background: Maternal exposure to inflammation is one of the causes of autism spectrum disorder (ASD). Electrical stimulation of the vagus nerve exerts a neuroprotective effect via its anti-inflammatory action. We thus investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) can enhance social abilities in a mouse model of ASD induced by maternal immune activation (MIA).

Methods: ASD mouse model were constructed by intraperitoneal injection of polyinosinic:polycytidylic acid (poly (I:C)). TaVNS with different parameters were tested in ASD mouse model and in C57BL/6 mice, then various behavioral tests and biochemical analyses related to autism were conducted. ASD model mice were injected with an interleukin (IL)-17a antibody into the brain, followed by behavioral testing and biochemical analyses.

Results: TaVNS reduced anxiety, improved social function, decreased the number of microglia, and inhibited M1 polarization of microglia. Additionally, taVNS attenuated the expression of the IL-17a protein in the prefrontal cortex and blood of ASD model mice. To examine the possible involvement of IL-17a in taVNS-induced neuroprotection, we injected an IL-17a antibody into the prefrontal cortex of ASD model mice and found that neutralizing IL-17a decreased the number of microglia and inhibited M1 polarization. Furthermore, neutralizing IL-17a improved social function in autism model mice.

Conclusion: Our study revealed that reduced neuroinflammation is an important mechanism of taVNS-mediated social improvement and neuroprotection against autism. This effect of taVNS could be attributed to the inhibition of the IL-17a pathway.

Keywords: IL-17A; autism spectrum disorder; microglia; social ability; taVNS.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Key Realm R&D Program of Guangdong Province (2019B030335001 to ZC); the Government-enterprise Joint Programs of Natural Science Foundation of Guangdong Province (2021A1515220049 to ZM); and the Funding by Science and Technology Projects in Guangzhou (202201020046 to ZM).