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Postnatal survival of phrenic motor neurons is promoted by BDNF/TrkB.FL signaling.
Brandenburg, Joline E; Fogarty, Matthew J; Zhan, Wen-Zhi; Kopper, Leo A; Sieck, Gary C.
Afiliação
  • Brandenburg JE; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, Minnesota, United States.
  • Fogarty MJ; Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, United States.
  • Zhan WZ; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, United States.
  • Kopper LA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, United States.
  • Sieck GC; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, United States.
J Appl Physiol (1985) ; 136(5): 1113-1121, 2024 May 01.
Article em En | MEDLINE | ID: mdl-38511211
ABSTRACT
The number of motor neurons (MNs) declines precipitously during the final trimester before birth. Thereafter, the number of MNs remains relatively stable, with their connections to skeletal muscle dependent on neurotrophins, including brain-derived neurotrophic factor (BDNF) signaling through its high-affinity full-length tropomyosin-related kinase receptor subtype B (TrkB.FL) receptor. As a genetic knockout of BDNF leads to extensive MN loss and postnatal death within 1-2 days after birth, we tested the hypothesis that postnatal inhibition of BDNF/TrkB.FL signaling is important for postnatal phrenic MN (PhMN) survival. In the present study, we used a 1NMPP1-sensitive TrkBF616A mutant mouse to evaluate the effects of inhibition of TrkB kinase activity on phrenic MN (PhMN) numbers and diaphragm muscle (DIAm) fiber cross-sectional area (CSA). Pups were exposed to 1NMPP1 or vehicle (DMSO) from birth to 21 days old (weaning) via the mother's ingestion in the drinking water. Following weaning, the right phrenic nerve was exposed in the neck and the proximal end dipped in a rhodamine solution to retrogradely label PhMNs. After 24 h, the cervical spinal cord and DIAm were excised. Labeled PhMNs were imaged using confocal microscopy, whereas DIAm strips were frozen at ∼1.5× resting length, cryosectioned, and stained with hematoxylin and eosin to assess CSA. We observed an ∼34% reduction in PhMN numbers and increased primary dendrite numbers in 1NMPP1-treated TrkBF616A mice. The distribution of PhMN size (somal surface area) DIAm fiber cross-sectional areas did not differ. We conclude that survival of PhMNs during early postnatal development is sensitive to BDNF/TrkB.FL signaling.NEW & NOTEWORTHY During early postnatal development, BDNF/TrkB signaling promotes PhMN survival. Inhibition of BDNF/TrkB signaling in early postnatal development does not impact PhMN size. Inhibition of BDNF/TrkB signaling in early postnatal development does not impact the number or CSA of DIAm fibers.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nervo Frênico / Transdução de Sinais / Fator Neurotrófico Derivado do Encéfalo / Receptor trkB / Neurônios Motores Limite: Animals Idioma: En Revista: J Appl Physiol (1985) Assunto da revista: FISIOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nervo Frênico / Transdução de Sinais / Fator Neurotrófico Derivado do Encéfalo / Receptor trkB / Neurônios Motores Limite: Animals Idioma: En Revista: J Appl Physiol (1985) Assunto da revista: FISIOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos