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GDNF AND CISPLATIN NEURONOPATHY
Author(s) -
Cavaletti G.,
Dondè E.,
Marmiroli P.,
Tredici G.
Publication year - 2000
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1046/j.1529-8027.2000.00513-13.x
Subject(s) - glial cell line derived neurotrophic factor , neurotrophic factors , receptor , neurotrophin , trk receptor , neuroscience , dopaminergic , proto oncogene proteins c ret , dorsal root ganglion , nerve growth factor , biology , gdnf family of ligands , pharmacology , medicine , sensory system , dopamine
GDNF is a growth factor produced in the central nervous system by glial cells and has a trophic action on dopaminergic neurons. However, GDNF mRNA is expressed also in the dorsal root ganglia (DRG), suggesting that it may act as a neurotrophic factor on different neuronal populations. The three different GDNF receptor components are highly expressed in a group of small primary sensory neurons and these neurons do not express any of the specific Trk receptors for the neurotrophins. Furthermore, GDNF receptor expression has been also found in DRG neurons of all sizes, indicating that these cells too may be responsive to GDNF. We have, therefore, evaluated the possible neuroprotective effect of GDNF (1 mg/kg, s.c. three times a week, donated by Amgen Inc) against cisplatin (CDDP, 2 mg/Kg i.p. twice a week for 9 times) DRG neuronopathy. Using our experimental paradigm, GDNF had no positive effect with both electrophysiological and morphometric determinations. The lack of GDNF activity in preventing the signs of peripheral nerve involvement in CDDP neuronopathy with respect to NGF and NT3 may be explained by a different distribution of their specific receptors in DRG neurons. In fact, the specific NT‐3 Trk C receptor is mainly expressed by the large DRG neurons, which are prominently involved in cisplatin neuronopathy, while GDNF receptors are mainly, although not exclusively, expressed by small‐ and medium‐sized DRG neurons. Small‐ and medium‐sized DRG neurons are also involved in the pathological changes of cisplatin neuronopathy, but to a lesser degree than the large ones. Furthermore, GDNF, in other models of peripheral neuropathies, may be active in an indirect way, mediated by its capacity to activate macrophages and inflammatory responses.