Age-related resistance to α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-induced hippocampal lesion

This study compares the effects of acute α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) administration in the hippocampus in adult (3 months) and middle‐aged (15 months) rats at 15 days postinjection. Injection of 1 and 2.7 mM AMPA produced dose‐dependent neurodegeneration, assessed by Nissl staining; a glial reaction shown by glial fibrillary acidic protein immunocytochemistry; and calcification, revealed by alizarin red staining. Furthermore, at both doses, these alterations were significantly greater in 3‐month‐old rats. Finally, at AMPA 2.7 mM, no significant changes in the density of hippocampal parvalbumin‐ or calbindin‐immunoreactive neurons or in choline acetyltransferase, glutamate uptake, or GABA uptake activities were found in 15‐month‐old animals, whereas significant reductions in parvalbumin (–76%) and calbindin (–32%) immunostaining and in GABA uptake (–27%) were observed in 3‐month‐old animals compared to the respective sham‐operated or control animals. In conclusion, this study clearly demonstrates that in rats the vulnerability of hippocampal neurons and the glial and calcification reactions to AMPA‐induced injury decreased with age between 3 and 15 months. Our results also indicate that hippocampal cholinergic, glutamatergic, and GABAergic systems show an adaptive response to excitotoxic damage in both adult and middle‐aged animals. Hippocampus 10:296–304, 2000 © 2000 Wiley‐Liss, Inc.