Immunohistochemical localization of group I and II metabotropic glutamate receptors in control and amyotrophic lateral sclerosis human spinal cord: Upregulation in reactive astrocytes

Excitotoxicity, which is mediated by the excessive activation of glutamate receptors, has been implicated in the pathogenesis of amyotrophic lateral s clerosis (ALS). There is substantial information about the distribution and function of ionotropic glutamate receptors in the spinal cord, although th e role of metabotropic glutamate receptors (mGluRs) is poorly understood in this region of the brain, particularly under pathological conditions. We u sed immunocytochemistry to study the general distribution of group I and gr oup II mGluR immunoreactivity in the human spinal cord, as well as the cell -specific expression of these receptors. We also investigated whether mGluR expression was altered in the spinal cord of patients with sporadic and fa milial ALS. Immunocytochemical analysis of control human spinal cord demons trated that mGluR1 alpha and mGluR5 (group I mGluRs) were highly represente d in neuronal cells throughout the spinal cord. mGluR I a showed the highes t relative level of expression in ventral horn neurons (laminae VIII and IX ), whereas intense mGluR5 immunoreactivity was observed within the dorsal h orn (superficial laminae I and 11). Group 11 mGluRs (mGluR2/3) immunoreacti vity was mainly concentrated in the inner part of the lamina Il. With respe ct to specific neuronal populations, mGluR2/3 and mGluR5 appeared to be mos t frequently expressed in calbindin-containing and calretinin-containing ce lls, respectively. In control spinal cord only sparse astrocytes showed a w eak to moderate mGluR immunoreactivity. Regional differences in immunoreact ivity were apparent in ALS compared to control. In particular, mGluR expres sion was increased in reactive glial cells in both gray (ventral horn) and white matter of ALS spinal cord. Upregulation of mGluRs in reactive astrocytes may represent a critical mech anism for modulation of glial function and changes in glial-neuronal commun ication in the course of neurodegenerative diseases. (C) 2001 IBRO. Publish ed by Elsevier Science Ltd. All rights reserved.