title: Methylphenidate prevents high-fat diet (HFD)-induced learning/memory impairment in juvenile mice.
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.
authors: Division of Nutritional Sciences, University of Illinois, Urbana, IL, USA; Department of Pathology, Program in Integrative Immunology and Behavior, University of Illinois, Urbana, IL, USA.
authors: Melissa M
authors: MM
authors: Kaczmarczyk
authors: Agnieszka S
authors: AS
authors: Machaj
authors: Gabriel S
authors: GS
authors: Chiu
authors: Marcus A
authors: MA
authors: Lawson
authors: Stephen J
authors: SJ
authors: Gainey
authors: Jason M
authors: JM
authors: York
authors: Daryl D
authors: DD
authors: Meling
authors: Stephen A
authors: SA
authors: Martin
authors: Kristin A
authors: KA
authors: Kwakwa
authors: Andrew F
authors: AF
authors: Newman
authors: Jeffrey A
authors: JA
authors: Woods
authors: Keith W
authors: KW
authors: Kelley
authors: Yanyan
authors: Y
authors: Wang
authors: Michael J
authors: MJ
authors: Miller
authors: Gregory G
authors: GG
authors: Freund
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001007:Anxiety / Q000209:etiology / Q000517:prevention & control; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D000697:Central Nervous System Stimulants / Q000494:pharmacology / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003891:Desipramine / Q000494:pharmacology; D004041:Dietary Fats / Q000009:adverse effects*; D004298:Dopamine / Q000032:analysis; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology; D006719:Homovanillic Acid / Q000032:analysis; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000172:deficiency; D007859:Learning Disabilities / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control*; D008774:Methylphenidate / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000032:analysis; D009025:Morpholines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D044343:Overnutrition / Q000503:physiopathology / Q000523:psychology*; D010807:Physical Endurance / Q000187:drug effects; D000077593:Reboxetine; D053573:Receptors, Interleukin-1 Type I; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D016207:Cytokines; D004041:Dietary Fats; C583355:IL1R1 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D009025:Morpholines; D053573:Receptors, Interleukin-1 Type I; D015102:3,4-Dihydroxyphenylacetic Acid; D008774:Methylphenidate; D000077593:Reboxetine; D008995:Monoamine Oxidase; D003891:Desipramine; D004298:Dopamine; D006719:Homovanillic Acid
keywords: ADHD; BDNF; COMT; Catechol-O-methyltransferase; DA; DOPAC; Depressive-like behavior; Forced swim test; HFD; HPLC; HVA; IDO; IP; Indoleamine 2,3 dioxygenase; KO; LFD; MAO; Monoamine oxidase; NGF; PBS; Type 2 diabetes; WT; attention deficit/hyperactive disorder; brain derived neurotrophic factor; catechol-O-methyltransferase; dihydroxyphenylacetic acid; dopamine; high-fat diet; high-performance liquid chromatography; homovanillic acid; indoleamine 2,3 dioxygenase; intraperitoneal; knockout; low-fat diet; monoamine oxidase; nerve growth factor; phosphate buffered saline; wild type