Fructose-Induced Cognitive Impairment Co-occurs with Morphological Changes in Dendrites and Microglia of Male Rats

Abstract

Fructose consumption in adolescents is accompanied by increased incidence of childhood diabetes, metabolic disorder, and obesity that can last into adulthood. Adult male rats that consumed a high fructose diet (HFD) in adolescence have dysregulated emotional processing and upregulated gene expression of neuroinflammatory markers, yet downstream consequences on cognitive function in both sexes remain unknown. The current study aimed to determine the extent to which a HFD altered neural and microglial structure and function that may contribute to cognitive changes inmales and females. Wistar rats were fed either chow or a HFD (55% fructose) beginning on postnatal day (PND) 23 and for the duration of the study. As adults, fructose-fed males, but not females, displayed impaired cognitive flexibility on the Barnes maze task and had more reactive microglia and altered neuronal morphology throughout the dentate gyrus (DG) and CA3 regions of the hippocampus. These findings suggest that, in males, a HFD activates microglia which may contribute to functional deficits, possibly through altering dendritic structure making them disproportionally vulnerable to fructose compared to females.