Regenerating sensory neurones of diabetic rats express reduced levels of mRNA for GAP-43, gamma-preprotachykinin and the nerve growth factor receptors, trkA and p75NGFR.
Nerve growth factor (NGF) is considered to play a role in neurite outgrowth of small nerve fibres which express its high-affinity receptor, trkA. Nerve regeneration is delayed in diabetes mellitus following an experimental crush injury. In steady-state (i.e., in the absence of axotomy) diabetic rats also show reduced expression of NGF in certain target tissues. This study was designed to measure expression of messenger RNA (mRNA) coding for NGF and its receptors, trkA and p75NGFR, during nerve regeneration and degeneration in rats with streptozotocin-induced diabetes; mRNA coding for preprotachykinin A (the substance P precursor), whose expression is stimulated by NGF, and mRNA for growth-associated protein-43 (GAP-43) were also measured in blots from L4 + L5 (pooled unilaterally) dorsal root ganglia. Unexpectedly, distal stumps of diabetic injured sciatic nerve contained higher levels of NGF mRNA than those of control rats. In ipsilateral dorsal root ganglia of control animals, mRNA for trkA and preprotachykinin A were decreased and GAP-43 mRNA increased after nerve injury; mRNA for p75NGFR was decreased only 3 weeks after nerve transection. In diabetic rats, the levels of all of these mRNA, both in intact and lesioned dorsal root ganglia, were lower than those from control rats. These results suggest that regenerating sensory neurones of diabetic rats receive less NGF support in spite of enhanced NGF mRNA levels in distal stumps compared to non-diabetic rats. Reduced expression of its high-affinity receptor, trkA, in ganglia of diabetic rats might explain this discrepancy.
Maeda
K
K
Department of Pharmacology, Faculty of Medical Sciences, Queen Mary and Westfield College, London, UK.
Fernyhough
P
P
Tomlinson
D R
DR
D000818:Animals; D001345:Autoradiography; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D019922:GAP-43 Protein; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D013997:Time Factors
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D011505:Protein-Tyrosine Kinases