Effect of FK506 on neurotransmitter content and expression of GAP-43 in neurotoxin-lesioned peripheral sensory and sympathetic neurons.
It has previously been shown that the capsaicin-lesioned peptidergic sensory neurons and the 6-hydroxydopamine (6-OHDA)-lesioned sympathetic noradrenergic neurons represent a useful model to study neurotrophin-induced nerve regeneration in the adult rat. The present study was aimed at investigating if the immunosuppressant drug FK506 (tacrolimus) has neuroregeneratory properties in these capsaicin- or 6-OHDA-lesioned peripheral nerves. FK506 was injected in a dose of 0.5 mg/kg/day for 10 days or in a dose of 1.5 mg/kg/day for 7 days. One day after the last FK506 injection neurotransmitter content was investigated in selected tissues. The content of the sensory neuron marker peptide calcitonin gene-related peptide (CGRP) was reduced after the capsaicin treatment in the hind paw skin by 35-40% and in the dorsal lumbar spinal cord by 48%. The treatment with FK506 did not induce a recovery of the CGRP content. Following the 6-OHDA treatment the noradrenaline content was reduced by 50-62% in the hind paw skin and by 73% in the heart atrium. FK506 alone did not increase the noradrenaline levels, whereas an additional local intraplantar treatment with nerve growth factor recovered noradrenaline levels almost completely. The expression of a marker protein for growth processes in cells of sympathetic or sensory ganglia, growth-associated protein-43, was significantly increased by the FK506 treatment. This study demonstrated that despite a stimulatory effect of FK506 on the expression of a growth-associated protein a recovery of the transmitter content is not evident in peripheral small diameter sensory or postganglionic sympathetic neurons of the adult rat.
Zuber
Martina
M
Institute of Experimental and Clinical Pharmacology, University of Graz, Austria.
Donnerer
Josef
J
D000704:Analysis of Variance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000633:toxicity; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006325:Heart Atria / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D017403:In Situ Hybridization; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009928:Organ Specificity; D016627:Oxidopamine / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*
D019922:GAP-43 Protein; D007166:Immunosuppressive Agents; D009498:Neurotoxins; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D016627:Oxidopamine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D016559:Tacrolimus