Zhang Wenjing, Mou Zhiwei, Zhong Qi, Liu Xiaocao, Yan Lan, Gou Lei, Chen Zhuoming, So Kwok-Fai, Zhang Li
Department of Rehabilitation Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Department of Rehabilitation Medicine, The Fifth Affiliated Hospital of Jinan University, Heyuan, China.
Front Psychiatry. 2024 Jun 27;15:1393549. doi: 10.3389/fpsyt.2024.1393549. eCollection 2024.
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).
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.
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.
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.
母亲暴露于炎症是自闭症谱系障碍（ASD）的病因之一。迷走神经电刺激通过其抗炎作用发挥神经保护作用。因此，我们研究了经皮耳迷走神经刺激（taVNS）是否能增强由母体免疫激活（MIA）诱导的ASD小鼠模型的社交能力。
通过腹腔注射聚肌苷酸:聚胞苷酸（poly (I:C)）构建ASD小鼠模型。在ASD小鼠模型和C57BL/6小鼠中测试不同参数的taVNS，然后进行各种与自闭症相关的行为测试和生化分析。给ASD模型小鼠脑内注射白细胞介素（IL）-17a抗体，随后进行行为测试和生化分析。
taVNS降低了焦虑，改善了社交功能，减少了小胶质细胞数量，并抑制了小胶质细胞的M1极化。此外，taVNS减弱了ASD模型小鼠前额叶皮质和血液中IL-17a蛋白的表达。为了研究IL-17a在taVNS诱导的神经保护中的可能作用，我们给ASD模型小鼠的前额叶皮质注射IL-17a抗体，发现中和IL-17a可减少小胶质细胞数量并抑制M1极化。此外，中和IL-17a改善了自闭症模型小鼠的社交功能。
我们的研究表明，神经炎症的减轻是taVNS介导的社交改善和针对自闭症的神经保护的重要机制。taVNS的这种作用可能归因于对IL-17a途径的抑制。
