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Review
. 2023 Dec 20;9(1):29.
doi: 10.1186/s42234-023-00132-3.

The brain-liver cholinergic anti-inflammatory pathway and viral infections

Samuel Martínez-Meza  1 , Bhavya Singh  2 , Douglas F Nixon  2 , Nicholas Dopkins #  2 , Louie Mar A Gangcuangco #  3
Affiliations
Review

The brain-liver cholinergic anti-inflammatory pathway and viral infections

Samuel Martínez-Meza et al. Bioelectron Med. .

Abstract

Efferent cholinergic signaling is a critical and targetable source of immunoregulation. The vagus nerve (VN) is the primary source of cholinergic signaling in the body, and partially innervates hepatic functionality through the liver-brain axis. Virus-induced disruption of cholinergic signaling may promote pathogenesis in hepatotropic and neurotropic viruses. Therefore, restoring VN functionality could be a novel therapeutic strategy to alleviate pathogenic inflammation in hepatotropic and neurotropic viral infections alike. In this minireview, we discuss the physiological importance of cholinergic signaling in maintaining liver-brain axis homeostasis. Next, we explore mechanisms by which the VN is perturbed by viral infections, and how non-invasive restoration of cholinergic signaling pathways with bioelectronic medicine (BEM) might ameliorate hepatic inflammation and neuroinflammation in certain viral infections.

Keywords: Bioelectronic medicine; Cholinergic signaling; Liver-brain axis; Vagus nerve; Viral infection.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

No competing interests.

Figures

Fig. 1
Fig. 1
Proposed model of viral disruption to acetylcholine-mediated immune hepatic homeostasis. Essential components of the cholinergic anti-inflammatory pathway, including the molecular events in the spleen and liver are presented. Viruses such as SARS-CoV-2 potentially enter the central nervous system (CNS) through transneural migration via the vagus nerve (VN). Essential components of the cholinergic anti-inflammatory pathway, including the molecular events in the spleen and liver are presented (A). In HIV-1 infection, degradation of nerve fibers regulating norepinephrine (NE) uptake may contribute to autonomic and peripheral nervous system comorbidities commonly observed in people living with HIV-1 (PLWH) (B and C)
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