Impairment of Long-term Memory by a Short-term High-fat Diet via Hippocampal Oxidative Stress and Alterations in Synaptic Plasticity

Abstract

Excessive dietary fat intake is considered a great risk factor for metabolic disorders as well as cognitive dysfunction. However, the potential mechanisms underlying the effects of a high-fat diet (HFD) on the brain remain rather obscure. The purpose of this study was to address how early exposure to HFD induces biochemical changes in different brain regions and affects short- and long-term memory. Mice were fed HFD or normal chow for 4 or 7 weeks beginning in adulthood. Our results showed that oxidative stress and biochemical alterations first appeared in the hippocampus after 4 weeks of exposure and were aggravated by a longer exposure time. Additionally, the HFD-fed mice displayed long-term memory impairments, but the performance of the mice in both the HF-4W and HF-7W groups on behavioral tests relying on short-term memory was not affected. The effect of HFD on the brain was also assessed by electrophysiology, which detected a gradual decrease in long-term potentiation in the CA1 region of the hippocampus. The abnormal expression of proteins associated with synaptic function, e.g. synaptophysin, CaMKII, CaMKIV, calcineurin A, ERK and c-fos, was observed in the hippocampus in response to HFD. These results indicate that HFD elicits rapid biochemical and neurological abnormalities in the hippocampus that contribute to cognitive defects and are potentially connected to the HFD-induced suppression of brain activity.

Keywords: biochemical alteration; high-fat diet; long-term memory; oxidative stress; synaptic plasticity.