Medizinische Universität Graz - Research portal
Selected Publication:
Zuber, M; Donnerer, J.
Effect of FK506 on neurotransmitter content and expression of GAP-43 in neurotoxin-lesioned peripheral sensory and sympathetic neurons.
Pharmacology. 2002; 66(1):44-50
Doi: 10.1159/000063254
Web of Science
PubMed
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FullText_MUG
- Leading authors Med Uni Graz
- Donnerer Josef
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Analysis of Variance -
- Animals -
- Calcitonin Gene-Related Peptide - metabolism
- Capsaicin - toxicity
- GAP-43 Protein - genetics
- Ganglia, Sympathetic - cytology
- Heart Atria - metabolism
- Immunosuppressive Agents - pharmacology
- In Situ Hybridization - pharmacology
- Male - pharmacology
- Neurons, Afferent - drug effects
- Neurotoxins - toxicity
- Neurotransmitter Agents - metabolism
- Organ Specificity - metabolism
- Oxidopamine - toxicity
- RNA, Messenger - metabolism
- Rats - metabolism
- Rats, Sprague-Dawley - metabolism
- Spinal Cord - metabolism
- Tacrolimus - pharmacology
- Find related publications in this database (Keywords)
- FK506
- nerve growth factor
- sensory afferents
- postganglionic sympathetic neurons
- growth-associated protein-43
- regeneration