title: Insulin rescues amyloid beta-induced impairment of hippocampal long-term potentiation.
abstract: Cerebral accumulation of amyloid beta-protein (Abeta) is generally believed to play a critical role in the pathogenesis of Alzheimer's disease (AD). Recent evidence suggests that Abeta-induced synaptic dysfunction is one of earliest pathogenic events observed in AD. Here we report that synthetic Abeta(1-42) strongly inhibited the induction of long-term potentiation (LTP) in the CA1 region of rat hippocampal slices. To ascertain which Abeta(1-42) sequences contribute to the impairment of LTP, we compared actions of several Abeta fragments and found that the sequence within 25-35 region of Abeta mainly contributes to the expression of LTP impairment. Importantly, we show that insulin and insulin-like growth factor-1 significantly inhibit Abeta oligomer formation, particularly dimers and trimers, and ameliorate the synthetic Abeta-induced suppression of LTP. Furthermore, dithiothreitol was found to be capable of significantly preventing the inhibitory effect of insulin on Abeta oligomer formation. In contrast, hemoglobin promotes Abeta oligomer formation and enhances Abeta-mediated inhibition of LTP induction. These results suggest that insulin may have utility in treating the earliest stages of Abeta-induced synaptic dysfunction in AD patients.
authors: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
authors: Cheng-Che
authors: CC
authors: Lee
authors: Yu-Min
authors: YM
authors: Kuo
authors: Chiung-Chun
authors: CC
authors: Huang
authors: Kuei-Sen
authors: KS
authors: Hsu
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D007328:Insulin