High-fat diet and aging-associated memory impairments persist in the absence of microglia in female rats

Sajida Malik; Soniya Xavier; Alita Soch; Simin Younesi; Jackson Yip; Mary Slayo; Ruth M Barrientos; Luba Sominsky; Sarah J Spencer

doi:10.1016/j.neurobiolaging.2024.04.010

High-fat diet and aging-associated memory impairments persist in the absence of microglia in female rats

Neurobiol Aging. 2024 May 1:140:22-32. doi: 10.1016/j.neurobiolaging.2024.04.010. Online ahead of print.

Authors

Sajida Malik¹, Soniya Xavier², Alita Soch³, Simin Younesi⁴, Jackson Yip², Mary Slayo⁵, Ruth M Barrientos⁶, Luba Sominsky⁷, Sarah J Spencer⁸

Affiliations

¹ School of Health and Biomedical Sciences RMIT University, Melbourne, VIC, Australia; IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia.
² School of Health and Biomedical Sciences RMIT University, Melbourne, VIC, Australia.
³ School of Health and Biomedical Sciences RMIT University, Melbourne, VIC, Australia; The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
⁴ School of Health and Biomedical Sciences RMIT University, Melbourne, VIC, Australia; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
⁵ School of Health and Biomedical Sciences RMIT University, Melbourne, VIC, Australia; Institute of Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, Germany; Center for Mind, Brain and Behavior-CMBB, Giessen, Marburg, Germany.
⁶ Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA; Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA; Chronic Brain Injury Program, The Ohio State University, Columbus, OH, USA.
⁷ School of Health and Biomedical Sciences RMIT University, Melbourne, VIC, Australia; Barwon Health, Geelong, Victoria, Australia; IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia.
⁸ School of Health and Biomedical Sciences RMIT University, Melbourne, VIC, Australia. Electronic address: Sarah.Spencer@rmit.edu.au.

PMID: 38703636
DOI: 10.1016/j.neurobiolaging.2024.04.010

Abstract

Aging is associated with a priming of microglia such that they are hypersensitive to further immune challenges. As such high-fat diet during aging can have detrimental effects on cognition that is not seen in the young. However, conflicting findings also suggest that obesity may protect against cognitive decline during aging. Given this uncertainty we aimed here to examine the role of microglia in high-fat, high-sucrose diet (HFSD)-induced changes in cognitive performance in the aging brain. We hypothesised that 8 weeks of HFSD-feeding would alter microglia and the inflammatory milieu in aging and worsen aging-related cognitive deficits in a microglia-dependent manner. We found that both aging and HFSD reduced hippocampal neuron numbers and open field exploration; they also impaired recognition memory. However, the aging-related deficits occurred in the absence of a pro-inflammatory response and the deficits in memory performance persisted after depletion of microglia in the Cx3cr1-Dtr knock-in rat. Our data suggest that mechanisms additional to the acute microglial contribution play a role in aging- and HFSD-associated memory dysfunction.

Keywords: Aging; Female; High-fat diet; Inflammaging; Inflammation; Microglia.