Glyburide administration reduces anxiety-like behaviors and mild cognitive impairment induced by short-term high-fat diet feeding exhibiting a role for the hippocampus and amygdala

Abstract

Obesity-associated comorbidities such as cognitive impairment and anxiety-like behaviors have been an increasing burden to public health. Therefore we investigated the role that increased dietary fat intake from a high-fat diet (HFD) feeding (60% kcals from fat) compared to a low-fat diet (LFD) feeding (10% kcals from fat) has on these comorbidities. C57BL/6J mice were fed a LFD or HFD for three weeks starting at 3–4 weeks of age and administered either saline or glyburide i.p. prior to testing on novel object location (NOL), a hippocampal-sensitive task, novel object recognition (NOR), an amygdala-sensitive task, as well as the elevated zero maze (EZM). After 1 week of HFD feeding, animals administered glyburide did not recover object discrimination in NOR when compared to LFD controls but NOL remained unimpaired. However, glyburide administration recovered object discrimination in the NOR and NOL task after 3 weeks of HFD feeding when compared to LFD controls. HFD mice treated with glyburide after 3 weeks of feeding performed similarly to LFD treated animals on the EZM but differed within saline animals. After 1 week of HFD feeding, no impact on GSH:GSSG was observed however after 3 weeks of HFD reduced GSH:GSSG when compared to LFD in the amygdala and hippocampus. These data suggest that glyburide acts as a mediator of oxidative stress to reduce HFD-induced cognitive impairment and anxiety-like behaviors.