Roles of the synaptic molecules Hevin and SPARC in mouse neuromuscular junction development and repair

NEUROSCIENCE LETTERS

卷:746

Article

Brayman, Vanessa L.^1,2  Taetzsch, Thomas³  Miko, MacKenzie¹  Dahal, Shreyaska¹  Risher, W. Christopher⁴  Valdez, Gregorio^3,5,6,7 

[1] Virginia Tech Carilion, Fralin Biomed Res Inst, 2 Riverside Circle, Roanoke, VA 24016 USA

[2] Virginia Tech, Grad Program Translat Biol Med & Hlth, 1 Riverside Circle, Roanoke, VA 24016 USA

[3] Brown Univ, Dept Mol Biol Cellular Biol & Biochem, 70 Ship St, Providence, RI 02903 USA

[4] Marshall Univ, Dept Biomed Sci, Joan C Edwards Sch Med, 1 John Marshall Dr, Huntington, WV 25755 USA

[5] Brown Univ, Ctr Translat Neurosci, Robert J & Nancy D Carney Inst Brain Sci, Providence, RI 02903 USA

[6] Brown Univ, Brown Inst Translat Sci, Providence, RI 02903 USA

[7] Brown Univ, Dept Neurol, Warren Alpert Med Sch, Providence, RI 02903 USA

关键词: Synapse;    Neuromuscular junction;    Development;    Injury;    Skeletal muscle;    Extracellular matrix;   

DOI  :  10.1016/j.neulet.2021.135663

来源: Elsevier

【 摘 要 】

Hevin and secreted protein acidic and rich in cysteine (SPARC) are highly homologous matricellular proteins that function in concert to guide the formation of brain synapses. Here, we investigated the role of these glycoproteins in neuromuscular junction (NMJ) maturation, stability, and repair following injury. Hevin and SPARC mRNA levels in developing (postnatal day 9), adult (postnatal days 90 and 120), and injured (fibular nerve crush) skeletal muscles were assessed with qPCR. Muscle fiber size was analyzed in developing (P9) mice lacking SPARC, Hevin, and both SPARC and Hevin. NMJ morphology was assessed in developing (P9), adult (P90) and injured (fibular nerve crush) mice lacking SPARC, Hevin, and both SPARC and Hevin skeletal muscle. Hevin and SPARC are expressed in skeletal muscles and are upregulated following nerve injury. Hevin(-/-) mice exhibited delayed NMJ and muscle fiber development but displayed normal NMJ morphology in adulthood and accelerated NMJ reinnervation following nerve injury. Mice lacking SPARC displayed normal NMJ and muscle fiber development but exhibited smaller NMJs with fewer acetylcholine receptor islands in adulthood. Further, SPARC deletion did not result in overt changes in NMJ reformation following nerve injury. The combined deletion of Hevin and SPARC had little effect on NMJ phenotypes observed in single knockouts, however deletion of SPARC in combination with Hevin reversed deficiencies in muscle fiber maturation observed in Hevin(-/-) muscle. These results identify SPARC and Hevin as extracellular matrix proteins with roles in NMJ development and repair.

【 授权许可】

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