Available online 1 May 2024

Aging is associated with microglial priming.

High-fat diet during aging can have detrimental effects on cognition and memory.

However, obesity may also protect against cognitive decline during aging.

Both aging and HFSD impaired recognition memory and hippocampal neuron turnover.

Depletion of microglia did not rescue this effect.

Aging-related dysfunction occurs in the absence of a pro-inflammatory response.

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.

aging

female

high-fat diet

inflammaging

inflammation

microglia

© 2024 The Author(s). Published by Elsevier Inc.