INCREASE IN ALPHA-CGRP AND GAP-43 IN AGED MOTONEURONS - A STUDY OF PEPTIDES, GROWTH-FACTORS, AND CHAT MESSENGER-RNA IN THE LUMBAR SPINAL-CORD OF SENESCENT RATS WITH SYMPTOMS OF HINDLIMB INCAPACITIES

Sprague-Dawley rats develop progressive motor dysfunctions during the third year of life. We use this as a model to examine possible neurona l mechanism(s) that may cause motor impairments occuring during aging. In this study we have used indirect immunofluorescence histochemistry (IF) and in situ hybridization histochemistry (ISH) to study quantita tively and qualitatively the staining pattern and mRNA expression of c alcitonin gene-related peptide (alpha-CGRP), growth-associated protein 43 (GAP-43), and acidic fibroblast growth factor (aFGF) in spinal lum bar motoneurons of young adult (2-3 months) and aged (30 months) Sprag ue-Dawley rats. In addition, mRNAs encoding choline acetyltransferase (ChAT), beta-CGRP, and cholecystokinin (CCK) were analyzed. All aged r ats used in this study disclosed symptoms of hindlimb incapacity, rang ing from mild weight-bearing insufficiency to paralysis of the hind li mbs. The symptoms were confined to the musculature of the hindlimb and hip regions. Only a small number (similar to 15%) of the large motone urons that innervate the hindlimb muscles were lost in those aged rats that had clinical symptoms of hindlimb motor incapacities. The remain ing motoneurons expressed ChAT mRNA at levels similar to those of youn g adult rats. The vast majority of these motoneurons showed increased mRNA levels for alpha-CGRP and GAP-43. Aged motoneurons contained more CGRP like immunoreactivity (LI), but the number of immunoreactive neu rons was smaller than in adult rats. GAP-43-LI could be detected in mo toneurons in aged, but not in adult, rats. GAP-43-LI was always coloca lized with CGRP-LI in aged motoneurons. Studies of individual aged rat s revealed that the increase of GAP-43 mRNA-positive cell bodies occur red in cases with the most severe clinical symptoms, whereas the incre ase in alpha-CGRP was even evident in rats with mild symptoms. No alte rations in content of aFGF-LI or aFGF mRNA could be detected in the ag ed rat, and the content of CCK and beta-CGRP mRNAs was also normal. Th e usefulness of this rat model for studies of neuromuscular aging and possible functional roles for GAP-43 and CGRP in plastic and regenerat ive processes during aging are discussed. (C) 1995 Wiley-Liss, Inc.