Calcitonin gene-related peptide- 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)-immunoreactive (IR) axons in the nucleus gracilis of normal rats (1-15 months of age) were studied by light and electron microscopy. Besides many CGRP-IR and SP-IR varicosities with normal appearance, we found a few swollen (nearly round or oval) varicosities with either CGRP or SP immunoreactivity. Swollen CGRP-IR varicosities were more frequently seen than SP-IR ones, appearing from 3 months of age and increasing in number and size (up to approximately 25 microns in diameter) with advancing age. At the electron microscopic (EM) level, CGRP-IR and SP-IR swollen varicosities 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 made synaptic contacts with nonreactive dendrites (occasionally with non-IR axons). These findings suggest that the dystrophic CGRP and SP axonal 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-IR axons were identified to be SP-IR. However, no single dystrophic varicosity was found to contain both CGRP and SP immunoreactivities. These findings suggest that CGRP and SP afferents are independently affected and progress to dystrophic changes.