Effect of nerve growth factor on peptide neurons in dorsal root ganglia after taxol or cisplatin treatment and in diabetic (db/db) mice.
In our study we have used morphological and radio-immunological methods for the investigation of calcitonin gene-related peptide (CGRP) and substance P in cervical dorsal root ganglia (DRGs) in mice after administration of taxol or cisplatin and in spontaneously diabetic animals (db/db mice). The results were compared to findings in animals receiving recombinant human nerve growth factor (rhNGF). Morphometric analysis did not reveal any significant changes of cell size distribution in diabetic and taxol-treated mice, whereas cisplatin induced a significant decrease in the number of large- and medium-sized neurons, indicating neuronal atrophy. This finding correlated with a highly significant loss of neuropeptides after cisplatin-application. Measurement of peptide levels in the taxol-treated groups and in diabetic mice demonstrated a decrease predominantly for CGRP. Application of 10 mg/kg NGF caused a significant elevation in peptide-immunoreactivity in control animals and in taxol-treated mice, i.e., statistically significant increase in peptide concentrations and in the number of substance P- and CGRP-immunoreactive DRG-neurons, suggesting a recruitment of additional peptide cells. In diabetic animals a restoration in CGRP-content was observed under NGF-treatment; however, in this model the quantitative parameters did not demonstrate further elevation above control levels. Our data support the hypothesis that NGF exerts a major effect on the metabolism of transmitters associated with nociception and sensation in "healthy" controls and in various models of toxic and metabolic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
Schmidt
Y
Y
Department of Anatomy, University of Munich, Germany.
Unger
J W
JW
Bartke
I
I
Reiter
R
R
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D003929:Diabetic Neuropathies / Q000378:metabolism* / Q000473:pathology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology*; D013373:Substance P / Q000378:metabolism
D009414:Nerve Growth Factors; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D017239:Paclitaxel; D002945:Cisplatin