Effects of the neurotrophic agent T-817MA on oligomeric amyloid-β-induced deficits in long-term potentiation in the hippocampal CA1 subfield

Formation of oligomeric amyloid-beta (oA beta) is 1 of the most likely causes of Alzheimer's disease (AD). We hypothesized that in the early phase of AD, cognitive impairments observed before marked neuronal loss and brain atrophy might be associated with oA beta-induced synaptic dysfunction. T-817MA [1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate] has both neuroprotective and neurotrophic effects and is used to treat AD. Although T-817MA has been shown to ameliorate amyloid-induced learning deficits in experimental AD models, it remains unclear whether this drug would be able to prevent oA beta-induced synaptotoxicity. In the present study, we investigated the effects of T-817MA on the disturbances in synaptic plasticity induced by oA beta 42 and oligomeric photo-cross-linked A beta 42 (oXLA beta 42) in a slice preparation of the CA1 subfield of mouse hippocampus. Both oA beta 42 and oXLA beta 42 treatments significantly reduced the induction of long-term potentiation (LTP). In addition, oAb42 treatment significantly facilitated long-term depression (LTD). Treatment with T-817MA ameliorated the LTP reduction; however, T-817MA treatment did not inhibit the facilitation of LTD induction by oAb42. These results suggest that T-817MA reverses oAb-induced LTP reduction as it may occur in the early phase of AD. (C) 2014 Elsevier Inc. All rights reserved.