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

This study compares the effects of acute alpha-amino-3-hydroxy-5-methyl-4-i soxazole propionic acid (AMPA) administration in the hippocampus in adult ( 3 months) and middle-aged (15 months) rats at 15 days postinjection. Inject ion of 1 and 2.7 mM AMPA produced dose-dependent neurodegeneration, assesse d by Nissl staining; a glial reaction shown by glial fibrillary acidic prot ein immunocytochemistry; and calcification, revealed by alizarin red staini ng. Furthermore, at both doses, these alterations were significantly greate r in 3-month-old rats, Finally, at AMPA 2.7 mM, no significant changes in t he density of hippocampal parvalbumin- or calbindin-immunoreactive neurons or in choline acetyltransferase, glutamate uptake, or GABA uptake activitie s were found in 15-month-old animals, whereas significant reductions in par valbumin (-76%) and calbindin (-32%) immunostaining and in GABA uptake (-27 %) were observed in 3-month-old animals compared to the respective sham-ope rated or control animals. In conclusion, this study clearly demonstrates th at in rats the vulnerability of hippocampal neurons and the glial and calci fication reactions to AMPA-induced injury decreased with age between 3 and 15 months. Our results also indicate that hippocampal cholinergic, glutamat ergic, and GABAergic systems show an adaptive response to excitotoxic damag e in both adult and middle-aged animals. (C) 2000 Wiley-Liss, Inc.