Evaluation of the neuromuscular junction in a middle-aged mouse model of congenital myasthenic syndrome

Author(s):Show less -

Leite Schetino, Luana Pereira ^[1] ; Fonseca, Matheus de Castro ^[2] ; Simao Magalhaes Gomes, Matheus Proenca ^[3] ; Costa Valadao, Priscila Aparecida ^[3] ; de Camargo, Wallace Lucio ^[4] ; Rodrigues, Hermann Alecsandro ^[5] ; Andrade, Jessica Neves ^[3] ; Arantes-Costa, Fernanda Magalhaes ^[6] ; Naves, Ligia Araujo ^[4] ; Prado, Carla Maximo ^[7] ; Prado, Vania Ferreira ^{[8, 9]} ; Maximo Prado, Marco Antonio ^{[8, 9]} ; Guatimosim, Cristina ^[3]

Affiliation

^[1] Univ Fed Vales Jequitinhonha & Mucuri, Fac Med, Diamantina, MG - Brazil

^[2] Ctr Nacl Pesquisa Energia & Mat, Lab Nacl Biociencias, Campinas, SP - Brazil

^[3] Univ Fed Minas Gerais, Dept Morfol, Belo Horizonte, MG - Brazil

^[4] Univ Fed Minas Gerais, Dept Fisiol & Biofis, Belo Horizonte, MG - Brazil

^[5] Univ Fed Juiz de Fora, Inst Ciencias Vida, Dept Ciencias Basicas Vida, Campus Governador Valadares, Juiz De Fora, MG - Brazil

^[6] Univ Sao Paulo, Dept Med, Escola Med, Sao Paulo, SP - Brazil

^[7] Univ Fed Sao Paulo, Dept Biociencias, Campus Baixada Santista, Sao Paulo - Brazil

^[8] Univ Western Ontario, Robarts Res Inst, London, ON - Canada

^[9] Univ Western Ontario, Dept Physiol & Pharmacol & Anat & Cell Biol, London, ON - Canada

• Document type: Journal article
• Source: MUSCLE & NERVE; v. 60, n. 6, p. 790-800, DEC 2019.
• Web of Science Citations: 0

Abstract

Introduction Reduced expression of the vesicular acetylcholine transporter (VAChT) leads to changes in the distribution and shape of synaptic vesicles (SVs) at neuromuscular junctions (NMJs), suggesting vesicular acetylcholine (ACh) as a key component of synaptic structure and function. It is poorly understood how long-term changes in cholinergic transmission contribute to age- and disease-related degeneration in the motor system. Methods In this study we performed confocal imaging, electrophysiology, electron microscopy, and analyses of respiratory mechanics of the diaphragm NMJ components in 12-month-old wild-type (WT) and VAChTKD(HOM) mice. Results Diaphragms of NMJs of the VAChTKD(HOM) mice were similar to those in WT mice in number, colocalization, and fragmentation of pre-/postsynaptic components. However, they had increased spontaneous SV exocytosis, miniature endplate potential frequency, and diminished MEPP amplitude. No impairment in respiratory mechanics at rest was observed, probably due to the large neurotransmission safety factor of the diaphragm. Discussion The present findings help us to understand the consequences of reduced ACh release at the NMJs during aging. (AU)

• FAPESP's process: 18/20014-0 - The gut-brain connection: role of the gut microbioma in the outcome and development of the sporadic Parkinson's disease
• Grantee: Matheus de Castro Fonseca
• Support Opportunities: Regular Research Grants