Foxg1 Modulation of the Prkcd Gene in the Lateral Habenula Mediates Trigeminal Neuralgia-Associated Anxiety-Like Behaviors in Mice.

Autor: Aji A; Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Institute of Acupuncture Research, Fudan University, Shanghai, China., Zhang C; Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Institute of Acupuncture Research, Fudan University, Shanghai, China., Liu W; Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Institute of Acupuncture Research, Fudan University, Shanghai, China., Chen T; Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Institute of Acupuncture Research, Fudan University, Shanghai, China., Liu Z; Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Institute of Acupuncture Research, Fudan University, Shanghai, China., Zuo J; Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Institute of Acupuncture Research, Fudan University, Shanghai, China., Li H; Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Institute of Acupuncture Research, Fudan University, Shanghai, China., Mi W; Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Institute of Acupuncture Research, Fudan University, Shanghai, China., Mao-Ying QL; Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Institute of Acupuncture Research, Fudan University, Shanghai, China., Wang Y; Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Institute of Acupuncture Research, Fudan University, Shanghai, China.; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China., Zhao Q; Shanghai Sunshine Rehabilitation Center, Shanghai Yangzhi Rehabilitation Hospital, Tongji University School of Medicine, Shanghai, China. qingzhao2010@hotmail.com., Chu YX; Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Institute of Acupuncture Research, Fudan University, Shanghai, China. yuxiachu@fudan.edu.cn.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2024 Jul; Vol. 61 (7), pp. 4335-4351. Date of Electronic Publication: 2023 Dec 12.
DOI: 10.1007/s12035-023-03856-0
Abstrakt: Trigeminal Neuralgia (TN) is a debilitating disorder frequently accompanied by mood complications such as depression and anxiety. The current study sought to elucidate the molecular underpinnings that contribute to the pathogenesis of TN and its associated anxiety. Employing a partial transection of the infraorbital nerve (pT-ION) in a murine model, we successfully induced sustained primary and secondary orofacial allodynia alongside anxiety-like behavioral manifestations. Transcriptome-wide gene microarray analyses revealed a marked upregulation of Foxg1 subsequent to pT-ION. Targeted knockdown of Foxg1, achieved through bilateral microinjection of adeno-associated virus harboring Foxg1-specific shRNA into the lateral habenula (LHb), resulted in a significant attenuation of both orofacial pain and anxiety-like behaviors. Subsequent RNA sequencing implicated Prkcd as a downstream effector gene modulated by Foxg1. Pharmacological inhibition of protein kinase C delta, encoded by Prkcd, within the LHb markedly ameliorated pT-ION-induced symptomatology. The dual luciferase assay revealed that Foxg1 substantially enhances the transcriptional activity of the Prkcd gene. Collectively, these findings indicate that trigeminal nerve injury leads to Foxg1 upregulation in the LHb, which in turn elevates the expression of Prkcd, culminating in the manifestation of orofacial pain and anxiety-like behaviors. This work offers promising therapeutic targets and a conceptual framework for the clinical management of TN and its psychological comorbidities.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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