Effects of nerve growth factor on expression of GAP-43 in right atria after sympathectomy in diabetic rats.
OBJECTIVE
The present study investigated the role of nerve growth factor (NGF) in the regeneration of noradrenergic nerves of right atria (following 6-hydroxydopamine; 6-OHDA, 100 mg/kg, i.p.) from non-diabetic and 8-week diabetic rats.


RESULTS
In cryostat sections of the right atria, GAP-43 immunoreactivity was concentrated in nerve terminals, preterminal axons of the endocardium, epicardium and myocardium, as well as in nerve fibres innervating the blood vessels and ganglionic cells. In serial sections, all positive staining for GAP-43 showed immunoreactivity for the neuronal marker PGP-9.5. In untreated non-diabetic rats, the total GAP-43 immunoreactivity was reduced to 60% relative to pretreatment levels, at day 14 after 6-OHDA, as quantified by Western blotting. In diabetic rats, 6-OHDA treatment produced a marked increase in the levels of total GAP-43 at days 28 and 49. NGF treatment (1 mg/kg, s.c., 3 times/week, for 2 weeks) had no effect on the level of total GAP-43 in right atria from non-diabetic and diabetic rats before treatment with 6-OHDA. However, it normalized the reduced GAP-43 immunoreactivity observed in 6-OHDA-treated non-diabetic rats. Interestingly, NGF treatment alone produced an increase in GAP-43 phosphorylation relative to total GAP-43 in right atria from both non-diabetic (44%) and diabetic groups (42%).


CONCLUSIONS
These findings suggest that nerve terminals of the right atria retain, in the mature adult, the capacity for structural and functional plasticity. The expression of GAP-43 in right atria of control and diabetic rats was differentially affected by 6-OHDA treatment. In injured noradrenergic neurones of the right atria, NGF modified the expression of GAP-43 only in non-diabetic rats and not in diabetic rats.
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Division of Neuroscience, School of Biological Sciences, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Tomlinson
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D000284:Administration, Oral; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D019922:GAP-43 Protein / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D006325:Heart Atria / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D016627:Oxidopamine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013563:Sympathectomy, Chemical / Q000379:methods; D013565:Sympatholytics / Q000008:administration & dosage / Q000494:pharmacology
D019922:GAP-43 Protein; D009414:Nerve Growth Factors; D013565:Sympatholytics; D016627:Oxidopamine