Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor

Abstract

Schizophrenia is one of the most debilitating mental disorders and is aggravated by the lack of efficacious treatment. Although its etiology is unclear, epidemiological studies indicate that infection and inflammation during development induces behavioral, morphological, neurochemical, and cognitive impairments, increasing the risk of developing schizophrenia. The inflammatory hypothesis of schizophrenia is also supported by clinical studies demonstrating systemic inflammation and microglia activation in schizophrenic patients. Although elucidating the mechanism that induces this inflammatory profile remains a challenge, mounting evidence suggests that neuroimmune interactions may provide therapeutic advantages to control inflammation and hence schizophrenia. Recent studies have indicated that vagus nerve stimulation controls both peripheral and central inflammation via alpha-7 nicotinic acetylcholine receptor (α7nAChR). Other findings have indicated that vagal stimulation and α7nAChR-agonists can provide therapeutic advantages for neuropsychiatric disorders, such as depression and epilepsy. This review analyzes the latest results regarding: (I) the immune-to-brain pathogenesis of schizophrenia; (II) the regulation of inflammation by the autonomic nervous system in psychiatric disorders; and (III) the role of the vagus nerve and α7nAChR in schizophrenia.

Baroreflex stimulation attenuates central but not peripheral inflammation in conscious endotoxemic rats

“…Neurons also have cytokine receptors, suggesting an active bidirectional crosstalk between the immune and nervous systems (Wyss-Coray and Mucke, 2002). Additionally, cytokines have different functions in the central nervous system and can induce neurotoxicity, which appears to contribute to the physiopathology of psychiatric [depression, schizophrenia] and neurodegenerative diseases [Parkinson’s and Alzheimer’s diseases] (Allan and Rothwell, 2003; Corsi-Zuelli et al, 2017; Dantzer et al, 2008). Moreover, since inflammation in the central nervous system, particularly in the hypothalamus, has recently been shown to be intricately involved in the development and maintenance of hypertension (Khor and Cai, 2017), we suggest that the selective and central anti-inflammatory potential of ADN stimulation could be an additional mechanism involved in the baroreflex anti-hypertensive effects.…”

Nerve Stimulation: Immunomodulation and Control of Inflammation

“…4b). Experimental, epidemiological, and clinical trials show that nicotine inhibits inflammation in multiple disorders including ulcerative colitis, arthritis, sepsis, schizophrenia, and Alzheimer’s disease[96–99]. However, nicotine has many detrimental side effects limiting its clinical use[100, 101].…”

Neural networks and the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation in depression

“…The distal end of the splenic nerve releases norepinephrine, which inhibits the release of TNF-α by spleen macrophages through binding to the β2 adrenergic receptor of spleen lymphocytes that release ACh [92]. Recent review studies have also indicated both peripheral and central anti-inflammatory effects in taVNS, exerted via α7 nAChRs [93]. VNS might have an anti-inflammatory effect on central serotonin levels and affect the HPA axis and cortisol levels [94].…”