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Methylphenidate prevents high-fat diet (HFD)-induced learning/memory impairment in juvenile mice
Melissa M Kaczmarczyk1, Agnieszka S Machaj, Gabriel S Chiu
1Division of Nutritional Sciences, University of Illinois, Urbana, IL, USA; Department of Pathology, Program in Integrative Immunology and Behavior, University of Illinois, Urbana, IL, USA.
Insights
A high-fat diet rapidly affects juvenile mice
Area of Science:
- Neuroscience
- Behavioral Science
- Nutritional Science
Background:
- Childhood obesity and psychological conditions like ADHD are rising.
- Causality between overnutrition, obesity, and behavioral issues is debated.
Purpose of the Study:
- To investigate the impact of short-term high-fat diet (HFD) on juvenile mouse behavior and neurochemistry.
- To explore potential therapeutic interventions for diet-induced behavioral changes.
Main Methods:
- Juvenile mice were fed a HFD for 1-3 weeks.
- Behavioral tests included burrowing, wheel running, zero maze, Y-maze, and novel object recognition.
- Brain tissue analysis focused on dopamine, its metabolites, BDNF, and inflammatory cytokines.
Main Results:
- One week of HFD increased burrowing and wheel running but impaired learning, memory, and anxiety-like behaviors.
- HFD led to increased hippocampal and cortical homovanillic acid (HVA) and decreased cortical BDNF gene expression.
- Psychostimulant methylphenidate, but not antidepressants, ameliorated HFD-induced learning and memory deficits.
Conclusions:
- Short-term HFD rapidly alters dopamine metabolism and induces anxiety-like behaviors and learning impairments in juvenile mice.
- These effects occur before significant weight gain or pre-diabetes, suggesting overnutrition's direct role.
- Fat overnutrition may be a key factor in childhood psychological issues such as anxiety and ADHD.
Abstract:
The prevalence of childhood obesity has risen dramatically and coincident with this upsurge is a growth in adverse childhood psychological conditions including impulsivity, depression, anxiety and attention deficit/hyperactive disorder (ADHD). Due to confounds that exist when determining causality of childhood behavioral perturbations, controversy remains as to whether overnutrition and/or childhood obesity is important. Therefore, we examined juvenile mice to determine if biobehaviors were impacted by a short-term feeding (1-3wks) of a high-fat diet (HFD). After 1wk of a HFD feeding, mouse burrowing and spontaneous wheel running were increased while mouse exploration of the open quadrants of a zero maze, perfect alternations in a Y-maze and recognition of a novel object were impaired. Examination of mouse cortex, hippocampus and hypothalamus for dopamine and its metabolites demonstrated increased homovanillic acid (HVA) concentrations in the hippocampus and cortex that were associated with decreased cortical BDNF gene expression. In contrast, pro-inflammatory cytokine gene transcripts and serum IL-1α, IL-1β, TNF-α and IL-6 were unaffected by the short-term HFD feeding. Administration to mice of the psychostimulant methylphenidate prevented HFD-dependent impairment of learning/memory. HFD learning/memory impairment was not inhibited by the anti-depressants desipramine or reboxetine nor was it blocked in IDO or IL-1R1 knockout mice. In sum, a HFD rapidly impacts dopamine metabolism in the brain appearing to trigger anxiety-like behaviors and learning/memory impairments prior to the onset of weight gain and/or pre-diabetes. Thus, overnutrition due to fats may be central to childhood psychological perturbations such as anxiety and ADHD.
