Calcitonin gene-related peptide immunoreactivity in the hippocampus and its relationship to cellular changes...

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 this neuropeptide to be involved in neuronal protection and remodeling, vasodilation, immunomodulation, and apoptosis, thus making it an important constituent 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 because TMT causes dramatic changes in the endocrine system, the limbic system, particularly the hippocampus, as well as in the immune response. We have specifically focused on comparing the changes in CGRP-IR with the pattern of apoptosis (via TUNEL staining), cell-cycle activation (Ki67-IR), and in alteration in microglia (OX-42-IR) and astrocyte (gGFAP-IR) immunocytochemistry in TMT-treated hippocampus. Our results show a marked change in CGRP-IR in regions of the hippocampus that are temporally and anatomically correlated with the induction of apoptosis and activation of microglia, astrocyte, and the cell-cycle marker. Given the known effects of CGRP on these cell types and on programmed cell death elsewhere, these findings are consistent with a regional immunoregulatory/injury response role for CGRP following organotin poisoning.