Calcitonin gene-related peptide immunoreactivity in the hippocampus and its relationship to cellular changes following exposure to trimethyltin

Calcitonin gene-related peptide (CGRP) is a neuropeptide that is regionally regulated following peripheral insult and in central nervous system (CNS) damage models targeting limbic structures. Functional studies have shown th is neuropeptide to be involved in neuronal protection and remodeling, vasod ilation, immunomodulation, and apoptosis, thus making it an important const ituent of the acute phase response, In the present study, we characterized the anatomic expression and distribution of CGRP immunoreactivity (CGRP-IR) after exposure to the toxin, trimethyltin (TMT). We chose this model becau se TMT causes dramatic changes in the endocrine system, the limbic system, particularly the hippocampus, as well as in the immune response, We have sp ecifically focused on comparing the changes in CGRP-IR with the pattern of apoptosis (via TUNEL staining), cell-cycle activation (Ki67-IR), and in alt eration in microglia (OX-42-IR) and astrocyte (gGFAP-IR) immunocytochemistr y in TMT-treated hippocampus, Our results show a marked change in CGRP-IR i n regions of the hippocampus that are temporally and anatomically correlate d with the induction of apoptosis and activation of microglia, astrocyte, a nd the cell-cycle marker, Given the known effects of CGRP on these cell typ es and on programmed cell death elsewhere, these findings are consistent wi th a regional immunoregulatory/injury response role for CGRP following orga notin poisoning. J. Neurosci. Res. 55:441-457, 1999. (C) 1999 Wiley-Liss, I nc.