Agonists of peroxisome proliferator-activated receptor-γ attenuate the Aβ-mediated impairment of LTP in the hippocampus in vitro

The data we present here suggest that agonists of peroxisome proliferator-activated receptor-gamma (PPAR gamma) can attenuate the effects of beta-amyloid peptide (A beta). Alzheimer's disease is associated with elevated levels of A beta, and enhanced expression of PPAR gamma. In this study, we determined that application of A beta([1-40]) could impair hippocampal post-tetanic potentiation (PTP) and long-term potentiation (LTP) in vitro. We investigated the effects of PPAR gamma agonists; troglitazone, ciglitazone and 15-deoxy-Delta(12,14) prostaglandin J(2) (PGJ(2)) on synaptic transmission and plasticity in area CA1. Both ciglitazone and PGJ2 increased baseline synaptic transmission significantly, without altering paired-pulse facilitation. PGJ(2) 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 A beta([1-40])-mediated impairment of LTP. The effect of troglitazone on the A beta([1-40])-mediated impairment of UP was not reversed by the PPAR gamma antagonist, GW-9662. These findings demonstrate that PPAR gamma agonists attenuate the effects of A on LTP, and support the potential use of these agents to alleviate the symptoms of Alzheimer's disease. We also suggest that PPAR gamma agonists may regulate expression of hippocampal LTP in vitro. (c) 2005 Elsevier Ltd. All rights reserved.