CALCITONIN-GENE-RELATED PEPTIDE-IMMUNOREACTIVE AND SUBSTANCE-P-IMMUNOREACTIVE AXONS IN THE NUCLEUS GRACILIS OF THE RAT WITH SPECIAL REFERENCE TO AXONAL DYSTROPHY - LIGHT AND ELECTRON-MICROSCOPIC OBSERVATIONS

Calcitonin gene-related peptide (CGRP) and substance P (SP)-immunoreac tive (IR) axons in the nucleus gracilis of normal rats (1-15 months of age) were studied by light and electron microscopy. Besides many CGRP -LR and SP-IR varicosities with normal appearance, we found a few swol len (nearly round or oval) varicosities with either CGRP or SP immunor eactivity. Swollen CGRP-IR varicosities were more frequently seen than SP-IR ones, appearing from 3 months of age and increasing in number a nd size (up to approximately 25 mu m in diameter) with advancing age. At the electron microscopic (EM) level, CGRP-LR and SP-LR swollen vari cosities showed dystrophic changes, i.e., many membranous dense bodies , and proliferation of microtubules and neurofilaments. CGRP-IR or SP- IR dystrophic axons also contained many mitochondria and sometimes mad e synaptic contacts with nonreactive dendrites (occasionally with non- IR axons). These findings suggest that the dystrophic CGRP and SP axon al profiles represent a functionally distinct subpopulation of axonal dystrophy in the nucleus gracilis and use CGRP or SP as a neuroactive substance. Using a double-immunostaining method, many of normal CGRP-I R axons were identified to be SP-IR. However, no single dystrophic var icosity was found to contain both CGRP and SP immunoreactivities. Thes e findings suggest that CGRP and SP afferents are independently affect ed and progress to dystrophic changes.