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Vagus nerve stimulation inhibits cortical spreading depression via glutamate-dependent TrkB activation mechanism in the nucleus tractus solitarius.
Liu, Tzu-Ting; Chen, Shih-Pin; Wang, Shuu-Jiun; Yen, Jiin-Cherng.
Afiliación
  • Liu TT; Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Chen SP; Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Wang SJ; Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Yen JC; Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
Cephalalgia ; 44(2): 3331024241230466, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38329067
ABSTRACT

BACKGROUND:

Vagus nerve stimulation (VNS) was recently found to inhibit cortical spreading depression (CSD), the underlying mechanism of migraine aura, through activation of the nucleus tractus solitarius (NTS), locus coeruleus (LC) and dorsal raphe nucleus (DRN). The molecular mechanisms underlying the effect of VNS on CSD in these nuclei remain to be explored. We hypothesized that VNS may activate glutamate receptor-mediated tropomyosin kinase B (TrkB) signaling in the NTS, thereby facilitating the noradrenergic and serotonergic neurotransmission to inhibit CSD.

METHODS:

To investigate the role of TrkB and glutamate receptors in non-invasive VNS efficacy on CSD, a validated KCl-evoked CSD rat model coupled with intra-NTS microinjection of selective antagonists, immunoblot and immunohistochemistry was employed.

RESULTS:

VNS increased TrkB phosphorylation in the NTS. Inhibition of intra-NTS TrkB abrogated the suppressive effect of VNS on CSD and CSD-induced cortical neuroinflammation. TrkB was found colocalized with glutamate receptors in NTS neurons. Inhibition of glutamate receptors in the NTS abrogated VNS-induced TrkB activation. Moreover, the blockade of TrkB in the NTS attenuated VNS-induced activation of the LC and DRN.

CONCLUSIONS:

VNS induces the activation of glutamate receptor-mediated TrkB signaling in the NTS, which might modulate serotonergic and norepinephrinergic innervation to the cerebral cortex to inhibit CSD and cortical inflammation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Quinasas / Depresión de Propagación Cortical / Estimulación del Nervio Vago Límite: Animals Idioma: En Revista: Cephalalgia Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Quinasas / Depresión de Propagación Cortical / Estimulación del Nervio Vago Límite: Animals Idioma: En Revista: Cephalalgia Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido