Saini, J, Faroni, A, Reid, AJ, Mouly, V, Butler-Browne, G, Lightfoot, AP, McPhee, JS, Degens, H and Al-Shanti, N (2021) Cross-talk between motor neurons and myotubes via endogenously secreted neural and muscular growth factors. Physiological Reports, 9 (8). e14791. ISSN 2051-817X

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Abstract

Neuromuscular junction (NMJ) research is vital to advance the understanding of neuromuscular patho-physiology and development of novel therapies for diseases associated with NM dysfunction. In vivo, the micro-environment surrounding the NMJ has a significant impact on NMJ formation and maintenance via neurotrophic and differentiation factors that are secreted as a result of cross-talk between muscle fibers and motor neurons. Recently we showed the formation of functional NMJs in vitro in a co-culture of immortalized human myoblasts and motor neurons from rat-embryo spinal-cord explants, using a culture medium free from serum and neurotrophic or growth factors. The aim of this study was to assess how functional NMJs were established in this co-culture devoid of exogenous neural growth factors. To investigate this, an ELISA-based microarray was used to compare the composition of soluble endogenously secreted growth factors in this co-culture with an a-neural muscle culture. The levels of seven neurotrophic factors brain-derived neurotrophic factor (BDNF), glial-cell-line-derived neurotrophic factor (GDNF), insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), and vascular endothelial growth factor (VEGF) were higher (p < 0.05) in the supernatant of NMJ culture compared to those in the supernatant of the a-neural muscle culture. This indicates that the cross-talk between muscle and motor neurons promotes the secretion of soluble growth factors contributing to the local microenvironment thereby providing a favourable regenerative niche for NMJs formation and maturation.

Item Type:	Article
Uncontrolled Keywords:	Motor Neurons; Neuromuscular Junction; Cells, Cultured; Cell Line; Animals; Humans; Rats; Vascular Endothelial Growth Factor A; Nerve Growth Factors; Insulin-Like Growth Factor I; Signal Transduction; Muscle Fibers, Skeletal; cross-talk; motor neurons; muscle; neural growth factors; neuromuscular junction (NMJ); Animals; Cell Line; Cells, Cultured; Humans; Insulin-Like Growth Factor I; Motor Neurons; Muscle Fibers, Skeletal; Nerve Growth Factors; Neuromuscular Junction; Rats; Signal Transduction; Vascular Endothelial Growth Factor A; 0606 Physiology; 1103 Clinical Sciences; 1116 Medical Physiology
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Pharmacy & Biomolecular Sciences
Publisher:	Wiley
SWORD Depositor:	A Symplectic
Date Deposited:	11 May 2022 11:16
Last Modified:	11 May 2022 11:16
DOI or ID number:	10.14814/phy2.14791
URI:	https://researchonline.ljmu.ac.uk/id/eprint/16801

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