Partial denervation of the medial gastrocnemius muscle results in growth-associated protein-43 immunoreactivity in sprouting axons and Schwann cells.
Regeneration in the mammalian peripheral nervous system following nerve injury is associated with the upregulation of a developmentally regulated phosphoprotein, growth-associated protein-43 (GAP-43), in the injured neurons. We have examined whether uninjured adult neurons also express GAP-43 when they sprout. The model system investigated has been the sprouting induced in the terminal axons of intact motor neurons by a partial muscle denervation. Partial denervation of the medial gastrocnemius muscle in adult rats was produced by resecting the terminal nerve supply to the anterolateral quadrant of the muscle. Three zones could be identified in the motor endplate region of the muscle after such a denervation using protein gene product (PGP) 9.5, calcitonin gene-related peptide and silver staining as axonal markers and S-100 to identify Schwann cells: a normally innervated zone, a totally denervated zone and a border or intermediate zone between the two which contained axons at the endplates with nodal and terminal sprouts. The endplates in the normally innervated zone were GAP-43 negative. In the denervated zone, Schwann cells were GAP-43 positive and had a distinctive appearance with a lack of any normal endplate organization. Endplates in the intermediate zone were GAP-43 immunoreactive. In approximately half, the GAP-43 immunoreactivity was axonal-like, identical to PGP 9.5 in an adjacent section; in the remainder it was Schwann cell-like, identical to S-100 staining. Partial muscle denervation results, therefore, in the appearance of GAP-43 both in axons and Schwann cells in the endplates bordering the denervated zone. The presence of GAP-43 in these cells may contribute to their capacity to sprout.
Mehta
A
A
Department of Anatomy and Developmental Biology, University College London, U.K.
Reynolds
M L
ML
Woolf
C J
CJ
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D005283:Fentanyl / Q000494:pharmacology; D019922:GAP-43 Protein; D006003:Glycogen / Q000378:metabolism; D006133:Growth Substances / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D009121:Muscle Denervation; D009132:Muscles / Q000201:enzymology / Q000294:innervation / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism*; D016622:Silver Staining; D013869:Thiolester Hydrolases / Q000378:metabolism; D043222:Ubiquitin Thiolesterase
D019922:GAP-43 Protein; D006133:Growth Substances; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009418:S100 Proteins; D006003:Glycogen; D000110:Acetylcholinesterase; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; D003975:Diazepam; D005283:Fentanyl