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-γ (PPARγ) can attenuate the effects of beta-amyloid peptide (Aβ). Alzheimer's disease is associated with elevated levels of Aβ, and enhanced expression of PPARγ. In this study, we determined that application of Aβ[1-40] could impair hippocampal post-tetanic potentiation (PTP) and long-term potentiation (LTP) in vitro. We investigated the effects of PPARγ agonists; troglitazone, ciglitazone and 15-deoxy-Δ12,14 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 Aβ[1-40]-mediated impairment of LTP. The effect of troglitazone on the Aβ[1-40]-mediated impairment of LTP was not reversed by the PPARγ antagonist, GW-9662. These findings demonstrate that PPARγ agonists attenuate the effects of Aβ on LTP, and support the potential use of these agents to alleviate the symptoms of Alzheimer's disease. We also suggest that PPARγ agonists may regulate expression of hippocampal LTP in vitro.