Agonists of peroxisome proliferator-activated receptor-gamma attenuate the Abeta-mediated impairment of LTP in the hippocampus in vitro.
The data we present here suggest that agonists of peroxisome proliferator-activated receptor-gamma (PPARgamma) can attenuate the effects of beta-amyloid peptide (Abeta). Alzheimer's disease is associated with elevated levels of Abeta, and enhanced expression of PPARgamma. In this study, we determined that application of Abeta([1-40]) could impair hippocampal post-tetanic potentiation (PTP) and long-term potentiation (LTP) in vitro. We investigated the effects of PPARgamma agonists; troglitazone, ciglitazone and 15-deoxy-delta(12,14) prostaglandin J2 (PGJ2) on synaptic transmission and plasticity in area CA1. Both ciglitazone and PGJ2 increased baseline synaptic transmission significantly, without altering paired-pulse facilitation. PGJ2 produced a significant reduction in LTP, whereas ciglitazone and troglitazone had no significant effect. In addition, prior application of each ligand attenuated the previously observed Abeta([1-40])-mediated impairment of LTP. The effect of troglitazone on the Abeta([1-40])-mediated impairment of LTP was not reversed by the PPARgamma antagonist, GW-9662. These findings demonstrate that PPARgamma agonists attenuate the effects of Abeta on LTP, and support the potential use of these agents to alleviate the symptoms of Alzheimer's disease. We also suggest that PPARgamma agonists may regulate expression of hippocampal LTP in vitro.
Costello
Derek A
DA
Department of Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
O'Leary
Deirdre M
DM
Herron
Caroline E
CE
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D047495:PPAR gamma / Q000819:agonists*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects
D016229:Amyloid beta-Peptides; D047495:PPAR gamma; C037112:9-deoxy-delta-9-prostaglandin D2; D015230:Prostaglandin D2