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 radioimmunological methods for the investigation of calcitonin gene-related peptide (CORP) and s ubstance P in cervical dorsal root ganglia (DRGs) in mice after admini stration of taxol or cisplatin and in spontaneously diabetic animals ( db/db mice). The results were compared to findings in animals receivin g recombinant human nerve growth factor (rhNGF). Morphometric analysis did not reveal any significant changes of cell size distribution in d iabetic and taxol-treated mice, whereas cisplatin induced a significan t decrease in the number of large- and medium-sized neurons, indicatin g neuronal atrophy. This finding correlated with a highly significant loss of neuropeptides after cisplatin-application. Measurement of pept ide levels in the taxol-treated groups and in diabetic mice demonstrat ed a decrease predominantly for CGRP. Application of 10 mg/kg NGF caus ed a significant elevation in peptide-immunoreactivity in control anim als and in taxol-treated mice, i.e., statistically significant increas e in peptide concentrations and in the number of substance P- and CGRP -immunoreactive DRG-neurons, suggesting a recruitment of additional pe ptide cells. In diabetic animals a restoration in CGRP-content was obs erved under NGF-treatment; however, in this model the quantitative par ameters did not demonstrate further elevation above control levels. Ou r data support the hypothesis that NGF exerts a major effect on the me tabolism of transmitters associated with nociception and sensation in ''healthy'' controls and in various models of toxic and metabolic neur opathy. In light of these results, the exogenous application of NGF ma y contribute to the restoration of neuronal function and integrity dur ing the course of sensory system disorders and may present a useful ap proach to the treatment of peripheral neuropathies. (C) 1995 Academic Press, Inc.