Short-Term High-Fat Diet (HFD) Induced Anxiety-Like Behaviors and Cognitive Impairment Are Improved with Treatment by Glyburide

• Published in: Frontiers in behavioral neuroscience Vol. 10; p. 156
• Main Authors: Gainey, Stephen J, Kwakwa, Kristin A, Bray, Julie K, Pillote, Melissa M, Tir, Vincent L, Towers, Albert E, Freund, Gregory G
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 11.08.2016; Frontiers Media S.A
• Subjects: Animal cognition; Anxiety; Behavior; Brain research; Cancer; Children; Cognition; Cognitive ability; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diet; Food; Glucose; Glyburide; High fat diet; Hippocampus; Insulin; Laboratories; Low fat diet; Memory; Neurogenesis; Neuroscience; Nutrient deficiency; Nutrition research; Obesity; Oils & fats; Oxidative Stress; Pattern recognition; Public health; Sulfonylurea; Traumatic brain injury; Weaning; Weight control; United States > US; anxiety; cognition; glyburide; oxidative stress; high-fat diet
• ISSN: 1662-5153; 1662-5153
• DOI: 10.3389/fnbeh.2016.00156

Obesity-associated comorbidities such as cognitive impairment and anxiety are increasing public health burdens that have gained prevalence in children. To better understand the impact of childhood obesity on brain function, mice were fed with a high-fat diet (HFD) from weaning for 1, 3 or 6 weeks. When compared to low-fat diet (LFD)-fed mice (LFD-mice), HFD-fed mice (HFD-mice) had impaired novel object recognition (NOR) after 1 week. After 3 weeks, HFD-mice had impaired NOR and object location recognition (OLR). Additionally, these mice displayed anxiety-like behavior by measure of both the open-field and elevated zero maze (EZM) testing. At 6 weeks, HFD-mice were comparable to LFD-mice in NOR, open-field and EZM performance but they remained impaired during OLR testing. Glyburide, a second-generation sulfonylurea for the treatment of type 2 diabetes, was chosen as a countermeasure based on previous data exhibiting its potential as an anxiolytic. Interestingly, a single dose of glyburide corrected deficiencies in NOR and mitigated anxiety-like behaviors in mice fed with HFD-diet for 3-weeks. Taken together these results indicate that a HFD negatively impacts a subset of hippocampal-independent behaviors relatively rapidly, but such behaviors normalize with age. In contrast, impairment of hippocampal-sensitive memory takes longer to develop but persists. Since single-dose glyburide restores brain function in 3-week-old HFD-mice, drugs that block ATP-sensitive K(+) (KATP) channels may be of clinical relevance in the treatment of obesity-associated childhood cognitive issues and psychopathologies.