Effects of thymol on amyloid-β-induced impairments in hippocampal synaptic plasticity in rats fed a high-fat diet

Abstract

Obesity and a high-fat diet (HFD) are known to increase the incidence of Alzheimer's disease (AD). Oxidative stress, a major risk factor for AD, is increased with HFD consumption. Thymol (Thy) has antioxidant properties. Therefore, in the present study, we examined the protective and therapeutic effects of Thy on amyloid-β (Aβ)-induced impairments in the hippocampal synaptic plasticity of HFD-fed rats. In this study, 72 adult male Wistar rats were randomly assigned to 9 groups (n = 8 rats/group): Group 1 (control; standard diet); Group 2: Control + phosphate-buffered saline (PBS) + Oil (Thy vehicle); Group 3 (HFD + PBS); Group 4: (HFD + Aβ); Group 5: Control + PBS + Thy; Group 6: (HFD + Aβ + Oil); Group 7: Control + Aβ + Thy; Group 8: HFD + PBS + Thy; Group 9: (HFD + Aβ + Thy). After stereotaxic surgery, the field potentials were recorded after the implantation of the recording and stimulating electrodes in the dentate gyrus (DG) and perforant pathway, respectively. Following high-frequency stimulation, the long-term potentiation (LTP) of the population spike (PS) amplitude and the slope of the excitatory postsynaptic potentials (EPSPs) were measured in the DG. The HFD rats that received Aβ exhibited a significant decrease in their EPSP slope and PS amplitude as compared to the control group. In contrast, Thy administration in the HFD + Aβ rats reduced the decrease in the EPSP slope and PS amplitude. Thy decreased the Aβ-induced LTP impairments in HFD rats. The HFD significantly increased serum malondialdehyde levels and decreased total antioxidant capacity and total glutathione levels; whereas, Thy supplementation significantly reversed these parameters. Therefore, these results suggest that Thy, a natural antioxidant, can be therapeutic against high risk factors for AD, such as HFD.

Keywords: Alzheimer’s disease; High-fat diet; Hippocampus; Long term potentiation; Thymol; β-Amyloid.