Dataset Information

High-Fat Diet Impairs Tactile Discrimination Memory in the Mouse.

ABSTRACT: Research on the impact of diet and memory has garnered considerable attention while exploring the link between obesity and cognitive impairment. High-fat diet (HFD) rodent models recapitulate the obesity phenotype and subsequent cognitive impairments. While it is known that HFD is associated with sensory impairment, little attention has been given to the potential role these sensory deficits may play in recognition memory testing, one of the most commonly used cognitive tests. Because mice utilize their facial whiskers as their primary sensory apparatus, we modified a common recognition test, the novel object recognition task, by replacing objects with sandpaper grits at ground level, herein referred to as the novel tactile recognition task (NTR). First, we tested whisker-manipulated mice in this task to determine its reliance on intact whiskers. Then, we tested the HFD mouse in the NTR. Finally, to ensure that deficits in the NTR are due to cognitive impairment and not HFD-induced sensory deficiencies, we tested the whisker sensitivity of HFD mice via the corner test. Our results indicate that the NTR is a whisker dependent task, and that HFD mice exhibit tactile recognition memory impairment, not accompanied by whisker sensory deficits.

SUBMITTER: Watson LS

PROVIDER: S-EPMC7129774 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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High-Fat Diet Impairs Tactile Discrimination Memory in the Mouse.

Watson Luke S LS Stone Tyler D TD Williams Dominique D Williams Alexus S AS Sims-Robinson Catrina C

Behavioural brain research 20200108

Research on the impact of diet and memory has garnered considerable attention while exploring the link between obesity and cognitive impairment. High-fat diet (HFD) rodent models recapitulate the obesity phenotype and subsequent cognitive impairments. While it is known that HFD is associated with sensory impairment, little attention has been given to the potential role these sensory deficits may play in recognition memory testing, one of the most commonly used cognitive tests. Because mice utili ...[more]

PMID: 31926214

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Project description:Vascular cognitive impairment (VCI) is the second most common cause of dementia. There is no treatment for VCI, in part due to a lack of understanding of the underlying mechanisms. The G-protein coupled receptor 39 (GPR39) is regulated by arachidonic acid (AA)-derived oxylipins that have been implicated in VCI. Furthermore, GPR39 is increased in microglia of post mortem human brains with VCI. Carriers of homozygous GPR39 SNPs have a higher burden of white matter hyperintensity, an MRI marker of VCI. We tested the hypothesis that GPR39 plays a protective role against high-fat diet (HFD)-induced cognitive impairment, in part mediated via oxylipins actions on cerebral blood flow (CBF) and neuroinflammation. Homozygous (KO) and heterozygous (Het) GPR39 knockout mice and wild-type (WT) littermates with and without HFD for 8 months were tested for cognitive performance using the novel object recognition (NOR) and the Morris water maze (MWM) tests, followed by CBF measurements using MRI. Brain tissue and plasma oxylipins were quantified with high-performance liquid chromatography coupled to mass spectrometry. Cytokines and chemokines were measured using a multiplex assay. KO mice, regardless of diet, swam further away from platform location in the MWM compared to WT and Het mice. In the NOR test, there were no effects of genotype or diet. Brain and plasma AA-derived oxylipins formed by 11- and 15-lipoxygenase (LOX), cyclooxygenase (COX) and non-enzymatically were increased by HFD and GPR39 deletion. Interleukin-10 (IL-10) was lower in KO mice on HFD than standard diet (STD), whereas IL-4, interferon γ-induced protein-10 (IP-10) and monocyte chemotactic protein-3 (MCP-3) were altered by diet in both WT and KO, but were not affected by genotype. Resting CBF was reduced in WT and KO mice on HFD, with no change in vasoreactivity. The deletion of GPR39 did not change CBF compared to WT mice on either STD or HFD. We conclude that GPR39 plays a role in spatial memory retention and protects against HFD-induced cognitive impairment in part by modulating inflammation and AA-derived oxylipins. The results indicate that GPR39 and oxylipin pathways play a role and may serve as therapeutic targets in VCI.

Project description:The transcription factor carbohydrate response element binding protein (ChREBP) has emerged as a crucial regulator of hepatic glucose and lipid metabolism. The increased ChREBP activity involves the pro-oncogenic PI3K/AKT/mTOR signaling pathway that induces aberrant lipogenesis, thereby promoting hepatocellular carcinomas (HCC). However, the molecular pathogenesis of ChREBP-related hepatocarcinogenesis remains unexplored in the high-fat diet (HFD)-induced mouse model. Male C57BL/6J (WT) and liver-specific (L)-ChREBP-KO mice were maintained on either a HFD or a control diet for 12, 24, and 48 weeks, starting at the age of 4 weeks. At the end of the feeding period, mice were perfused, and liver tissues were formalin-fixed, paraffin-embedded, sectioned, and stained for histological and immunohistochemical analysis. Biochemical and gene expression analysis were conducted using serum and frozen liver tissue. Mice fed with HFD showed a significant increase (p < 0.05) in body weight from 8 weeks onwards compared to the control. WT and L-ChREBP-KO mice also demonstrated a significant increase (p < 0.05) in liver-to-body weight ratio in the 48-week HFD group. HFD mice exhibited a gradual rise in hepatic lipid accumulation over time, with 24-week mice showing a 20-30% increase in fat content, which further advanced to 80-100% fat accumulation at 48 weeks. Both dietary source and the increased expression of lipogenic pathways at transcriptional and protein levels induced steatosis and steatohepatitis in the HFD group. Moreover, WT mice on a HFD exhibited markedly higher inflammation compared to the L-ChREBP-KO mice. The enhanced lipogenesis, glycolysis, persistent inflammation, and activation of the AKT/mTOR pathway collectively resulted in significant metabolic disturbances, thereby promoting HCC development and progression in WT mice. In contrast, hepatic loss of ChREBP resulted in reduced hepatocyte proliferation in the HFD group, which significantly contributed to the impaired hepatocarcinogenesis and a reduced HCC occurrence in the L-ChREBP-KO mice. Our present study implicates that prolonged HFD feeding contributes to NAFLD/NASH, which in turn progresses to HCC development in WT mice. Collectively, hepatic ChREBP deletion ameliorates hepatic inflammation and metabolic alterations, thereby impairing NASH-driven hepatocarcinogenesis.

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High-Fat Diet Impairs Tactile Discrimination Memory in the Mouse.

Publications

High-Fat Diet Impairs Tactile Discrimination Memory in the Mouse.

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