Dataset Information

A pharynx-to-brain axis controls pharyngeal inflammation-induced anxiety.

ABSTRACT: Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTS^NE). These NTS^NE neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynx→NJP→NTS^NE→vBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.

SUBMITTER: Zhao W

PROVIDER: S-EPMC10945766 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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A pharynx-to-brain axis controls pharyngeal inflammation-induced anxiety.

Zhao Wan W Zhang Ke K Dong Wan-Ying WY Tang Hao-Di HD Sun Jia-Qiang JQ Huang Ji-Ye JY Wan Guang-Lun GL Guan Rui-Rui RR Guo Xiao-Tao XT Cheng Ping-Kai PK Tao Ran R Sun Jing-Wu JW Zhang Zhi Z Zhu Xia X

Proceedings of the National Academy of Sciences of the United States of America 20240306 11

Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the ...[more]

PMID: 38446848

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Project description:In addition to the high neurotoxicity, depression, and anxiety are the most prominent characteristics of methamphetamine (Meth) withdrawal. Studies to date on the issue of Meth-associated depression and anxiety are focused on the brain, however, whether peripheral homeostasis, especially the "microbiota-gut" axis participates in these adverse outcomes, remains poorly understood. In the current study, with the fecal microbiota transplantation (FMT) assay, the mice received microbiota from Meth withdrawal mice displayed marked depression and anxiety behaviors. The 16S rRNA sequencing results showed that Meth withdrawal contributed to a striking reduction of Akkermansia, Bacteroides, Faecalibaculum, Desulfovibrio, and Anaerostipes, which are known to be associated with tryptophan (TRP) metabolism. Noteworthily, the substantial decreases of the indole derivatives from the TRP metabolic pathway, including IAA, IPA, ILA, IET, IArA, IAld, and TRM were observed in the serum of both Meth abusing humans and mice during Meth withdrawal with the UHPLC-MS/MS analysis. Combining the high and low TRP diet mouse model, the mice with high TRP diet obviously impeded Meth-associated depression and anxiety behaviors, and these results were further strengthened by the evidence that administration of IPA, IAA, and indole dramatically ameliorated the Meth induced aberrant behaviors. Importantly, these protective effects were remarkably counteracted in aryl hydrocarbon receptor knockout (AhR KO) mice, underlining the key roles of microbiota-indoles-AhR signaling in Meth-associated depression and anxiety. Collectively, the important contribution of the present work is that we provide the first evidence that peripheral gut homeostasis disturbance but not limited to the brain, plays a key role in driving the Meth-induced depression and anxiety in the periods of withdrawal, especially the microbiota and the indole metabolic disturbance. Therefore, targeting AhR may provide novel insight into the therapeutic strategies for Meth-associated psychological disorders.

Dataset Information

A pharynx-to-brain axis controls pharyngeal inflammation-induced anxiety.

Publications

A pharynx-to-brain axis controls pharyngeal inflammation-induced anxiety.

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