Difference in toxicity of beta-amyloid peptide with aging in relation to nerve growth factor content in rat brain.
Amyloid beta-peptide (Abeta) is the major constituent of the senile plaques in the brains of patients with Alzheimer's disease. We have demonstrated previously that memory impairment, dysfunction of the cholinergic and dopaminergic neuronal system and morphological degeneration are produced after the continuous infusion of Abeta into the cerebral ventricle in 8-week-old rat. In the present study, we investigated the toxicity of Abeta in infant (10 days old), adult (8 weeks old) and aged (20 months old) rats in relation to nerve growth factor (NGF) content in various regions of the brain. After a 2-week-infusion, choline acetyltransferase (ChAT) activity was significantly decreased in the hippocampus of adult, but not infant or aged rats. NGF levels in the hippocampus were increased only in adult rats. These results suggest that Abeta is toxic only in the matured adult brain, and that the mechanism of toxicity is related to NGF synthesis.
Fukuta
T
T
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan.
Nitta
A
A
Itoh
A
A
Furukawa
S
S
Nabeshima
T
T
D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D002795:Choline O-Acetyltransferase / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D008297:Male; D020932:Nerve Growth Factor / Q000032:analysis* / Q000096:biosynthesis; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase