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-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.
Bernal
F
F
Unitat de Bioquímica, IDIBAPS, Facultat de Medicina, Universitat de Barcelona, Spain.
Andrés
N
N
Samuel
D
D
Kerkerian-LeGoff
L
L
Mahy
N
N
D000375:Aging / Q000502:physiology*; D000818:Animals; D001692:Biological Transport; D015415:Biomarkers / Q000032:analysis; D064026:Calbindins; D002114:Calcinosis / Q000139:chemically induced / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D010320:Parvalbumins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000032:analysis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D015415:Biomarkers; D064026:Calbindins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002795:Choline O-Acetyltransferase