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

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.

Energy Restriction Enhances Adult Hippocampal Neurogenesis-Associated Memory after Four Weeks in an Adult Human Population with Central Obesity; a Randomized Controlled Trial

“…Evidence to suggest that the quality of diet and weight having a significant impact on cognition has increased substantially. For example, mice on a high fat diet display increased anxiety-like behavior and impaired learning [2,3]. Similar results can be seen in human populations.…”

Mori Cortex Radicis Attenuates High Fat Diet-Induced Cognitive Impairment via an IRS/Akt Signaling Pathway

“…In fact, the amount of insulin in hippocampus, hypothalamus, and cerebral cortex is 10-100 times that in plasma. Insulin also promotes neuronal cell growth and increases synapse plasticity [36]. Thus, insulin function in the central nervous system is related to homeostasis and proper brain function [5].…”

Effects of post-training administration of LY341495, as an mGluR2/3 antagonist on spatial memory deficit in rats fed with high-fat diet

“…Also, it has been shown that mGluRs are involved in various forms of synaptic plasticity in the hippocampus ( Bortolotto et al, 1999 ). Underwood and Thompson have found that HFD significantly reduces hippocampal intrinsic excitability in both young adult male and female Long-Evans rats ( Underwood and Thompson, 2016 ), and activation of group II mGluRs increases the hippocampal network activity ( Ster et al, 2011 ).…”