title: Spatial Cognition in Adult and Aged Mice Exposed to High-Fat Diet.
abstract: Aging is associated with a decline in multiple aspects of cognitive function, with spatial cognition being particularly sensitive to age-related decline. Environmental stressors, such as high-fat diet (HFD) exposure, that produce a diabetic phenotype and metabolic dysfunction may indirectly lead to exacerbated brain aging and promote the development of cognitive deficits. The present work investigated whether exposure to HFD exacerbates age-related cognitive deficits in adult versus aged mice. Adult (5 months old) and aged (15 months old) mice were exposed to control diet or HFD for three months prior to, and throughout, behavioral testing. Anxiety-like behavior in the light-dark box test, discrimination learning and memory in the novel object/place recognition tests, and spatial learning and memory in the Barnes maze test were assessed. HFD resulted in significant gains in body weight and fat mass content with adult mice gaining significantly more weight and adipose tissue due to HFD than aged mice. Weight gain was attributed to food calories sourced from fat, but not total calorie intake. HFD increased fasting insulin levels in all mice, but adult mice showed a greater increase relative to aged mice. Behaviorally, HFD increased anxiety-like behavior in adult but not aged mice without significantly affecting spatial cognition. In contrast, aged mice fed either control or HFD diet displayed deficits in novel place discrimination and spatial learning. Our results suggest that adult mice are more susceptible to the physiological and anxiety-like effects of HFD consumption than aged mice, while aged mice displayed deficits in spatial cognition regardless of dietary influence. We conclude that although HFD induces systemic metabolic dysfunction in both adult and aged mice, overall cognitive function was not adversely affected under the current experimental conditions.
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: James P
authors.initials: JP
authors.lastname: Kesby
authors.affiliation: Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Radiology, School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Miriam
authors.initials: M
authors.lastname: Scadeng
authors.affiliation: Department of Family Medicine & Public Health and Internal Medicine, School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Gina
authors.initials: G
authors.lastname: Woods
authors.affiliation: Department of Family Medicine & Public Health and Internal Medicine, School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Kado
authors.affiliation: Department of Family Medicine & Public Health and Internal Medicine, School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Jerrold M
authors.initials: JM
authors.lastname: Olefsky
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, California, United States of America; Sam and Rose Stein Institute for Research on Aging, School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Dilip V
authors.initials: DV
authors.lastname: Jeste
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, California, United States of America; Sam and Rose Stein Institute for Research on Aging, School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Cristian L
authors.initials: CL
authors.lastname: Achim
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Semenova
mesh_terms: D000818:Animals; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D007333:Insulin Resistance; D008297:Male; D018782:Maze Learning; D008810:Mice, Inbred C57BL; D015430:Weight Gain