High-fat diet impairs spatial memory and hippocampal intrinsic excitability and sex-dependently alters circulating insulin and hippocampal insulin sensitivity.

Erica L Underwood,Lucien T Thompson

doi:10.1186/s13293-016-0060-3

Abstract

BackgroundHigh-fat diets promoting obesity/type-2 diabetes can impair physiology and cognitive performance, although sex-dependent comparisons of these impairments are rarely made. Transient reductions in Ca2+-dependent afterhyperpolarizations (AHPs) occur during memory consolidation, enhancing intrinsic excitability of hippocampal CA1 pyramidal neurons. In rats fed standard diets, insulin can enhance memory and reduce amplitude and duration of AHPs.MethodsEffects of chronic high-fat diet (HFD) on memory, circulating insulin, and neuronal physiology were compared between young adult male and female Long-Evans rats. Rats fed for 12 weeks (from weaning) a HFD or a control diet (CD) were then tested in vivo prior to in vitro recordings from CA1 pyramidal neurons.ResultsThe HFD significantly impaired spatial memory in both males and females. Significant sex differences occurred in circulating insulin and in the insulin sensitivity of hippocampal neurons. Circulating insulin significantly increased in HFD males but decreased in HFD females. While the HFD significantly reduced hippocampal intrinsic excitability in both sexes, CA1 neurons from HFD females remained insulin-sensitive but those from HFD males became insulin-insensitive.ConclusionsFindings consistent with these have been characterized previously in HFD or senescent males, but the effects observed here in young females are unique. Loss of CA1 neuronal excitability, and sex-dependent loss of insulin sensitivity, can have significant cognitive consequences, over both the short term and the life span. These findings highlight needs for more research into sex-dependent differences, relating systemic and neural plasticity mechanisms in metabolic disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-016-0060-3) contains supplementary material, which is available to authorized users.

Highlights

High-fat diets promoting obesity/type-2 diabetes can impair physiology and cognitive performance, sex-dependent comparisons of these impairments are rarely made
Males fed the high-fat diet (HFD) exhibited a 14.3 % reduction in spontaneous alternation compared to control diet (CD)-fed males (p = 0.0197) while HFD females exhibited a 13.7 % reduction in spatial memory performance (p = 0.0013)
We found additional significant impairments in spatial memory (Fig. 2) and significant HFD-induced impairments in basal intrinsic excitability (Figs. 3 and 4) of hippocampal CA1 pyramidal neurons from both males and females, a profile typically only seen in senescent memory-impaired rats [44, 45, 59,60,61]

Summary

Introduction

High-fat diets promoting obesity/type-2 diabetes can impair physiology and cognitive performance, sex-dependent comparisons of these impairments are rarely made. Transient reductions in Ca2+-dependent afterhyperpolarizations (AHPs) occur during memory consolidation, enhancing intrinsic excitability of hippocampal CA1 pyramidal neurons. Underwood and Thompson [1] found that young adult male LongEvans rats fed a high-fat diet (HFD) became obese and had elevated fasted blood glucose levels, elevated corticosterone, and impaired glucose tolerance, while females fed the same HFD exhibited only elevated corticosterone. Regardless of peripheral metabolism alterations, both sexes fed the HFD were impaired in a spatial-object recognition memory task indicative of impaired hippocampal function. This study further elucidates the sexually dichotomous effects of a HFD on hippocampal function by examining dietary effects on cognitive performance, neuronal intrinsic excitability, and insulin sensitivity. Considerable evidence exists for insulin’s potential role in hippocampal memory: IR mRNA is highly expressed in the hippocampus [6], immediate post-acquisition infusion of insulin into the hippocampus enhances passive-avoidance memory in rats [7], and IR expression is up-regulated (and IR-insulin binding increased) in rat CA1 neurons after spatial learning [6, 8, 9]

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