Effect of troxerutin on synaptic plasticity of hippocampal dentate gyrus neurons in a ?-amyloid model of Alzheimer?s disease: an electrophysiological study.

Abstract

Alzheimer?s disease (AD) is a neurodegenerative disorder with a progressive cognitive decline and memory loss. Multiple pathogenetic factors including aggregated ?-amyloid (A?), neurofibrillary tangles (NFTs), cholinergic dysfunction and oxidative stress are involved in AD. A?, a major constituent of the senile plaques, is a potent neurotoxic peptide and has a pivotal role in cognitive deficit and reduced synaptic plasticity in AD. In the present study we examined the protective effect of troxerutin, as a multipotent bioflavonoid, on A? (1-42)-induced impairment of evoked field potential in hippocampal DG neurons. Male Wistar rats were divided into four groups including A? (42-1), A? (1-42), A? (1-42) plus troxerutin and A? (42-1) plus troxerutin groups. A? was injected intracerebroventricularly (i.c.v.) into right lateral ventricle and after two weeks the evoked field potential recorded from perforant path-DG synapses to assess paired pulse paradigm and long term potentiation (LTP). Administration of A? (1-42) drastically attenuated the LTP of DG neurons, while there was no significant difference in evoked field potentials between A? (1-42) plus troxerutin group with respect to A? (42-1) group. This study revealed that troxerutin improves the synaptic failure induced by A? peptide and can be introduced as a promising multi-potent pharmacological agent in prevention or treatment of AD in the future.