Immunohistochemical localization of GAP-43 in rat and human sympathetic nervous system--effects of aging and diabetes.
The neuronal 43 kDa growth associated peptide (GAP-43) is expressed in conditions of embryonic growth, axonal regeneration, and, to a limited degree, within the central nervous system as an indicator of synaptic plasticity. Although much is known about the expression of GAP-43 in cultured sympathetic neurons, information concerning the existence, immunolocalization and response of GAP-43 to experimental injury is not available for intact sympathetic ganglia in vivo. In this study we have characterized the in situ distribution and identity of GAP-43 in adult rat and human prevertebral and paravertebral sympathetic ganglia using immunohistochemical and biochemical methods. Antisera to GAP-43 intensely labeled intraganglionic presynaptic axons and synapses terminating on neurons of normal adult rat and human sympathetic ganglia in situ. There was minimal GAP-43 immunoreactivity of principal sympathetic neuron perikarya, proximal dendrites and initial axonal segments. The immunohistologic appearance of GAP-43 was unchanged in the ganglia of aged and diabetic rats and elderly humans, conditions in which presynaptic terminal axons and synapses show evidence of chronic degeneration, regeneration and neuroaxonal dystrophy, an unusual ultrastructural alteration which may represent disordered synaptic plasticity. Radioimmunoassay of ganglionic GAP-43 is comparable in young adult, aged and diabetic rat prevertebral or paravertebral sympathetic ganglia. Double immunolocalization of NPY (which labeled markedly swollen dystrophic axons) and GAP-43 in human sympathetic ganglia using a sequential immunogold-silver/fluorescence technique demonstrated that typical dystrophic axons contain little GAP-43.
Schmidt
R E
RE
Department of Pathology (Division of Neuropathology), Washington University School of Medicine, Saint Louis, MO 63110.
Spencer
S A
SA
Coleman
B D
BD
Roth
K A
KA
D000368:Aged; D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D005455:Fluorescent Antibody Technique; D019922:GAP-43 Protein; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000254:growth & development* / Q000473:pathology; D006133:Growth Substances / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009478:Neuropeptide Y / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D015415:Biomarkers; D019922:GAP-43 Protein; D006133:Growth Substances; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y