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Inter-relationships among diet, obesity and hippocampal-dependent cognitive function.

Abstract

Intake of a Western diet (WD), which is high in saturated fat and sugar, is associated with deficits in hippocampal-dependent learning and memory processes as well as with markers of hippocampal pathology. In the present study, rats were trained to asymptote on hippocampal-dependent serial feature negative (FN) and hippocampal-independent simple discrimination problems. Performance was then assessed following 7 days on ad libitum chow and after 10, 24, 40, 60, and 90 days of maintenance on WD, on ketogenic (KETO) diet, which is high in saturated fat and low in sugar and other carbohydrates, or continued maintenance on chow (CHOW). Confirming and extending previous findings, diet-induced obese (DIO) rats fed WD showed impaired FN performance, increased blood-brain barrier (BBB) permeability, and increased fasting blood glucose levels compared to CHOW controls and to diet-resistant (DR) rats that did not become obese when maintained on WD. For rats fed the KETO diet, FN performance and BBB integrity were more closely associated with level of circulating ketone bodies than with obesity phenotype (DR or DIO), with higher levels of ketones appearing to provide a protective effect. The evidence also indicated that FN deficits preceded and predicted increased body weight and adiposity. This research (a) further substantiates previous findings of WD-induced deficits in hippocampal-dependent FN discriminations, (b) suggests that ketones may be protective against diet-induced cognitive impairment, and (c) provides evidence that diet-induced cognitive impairment precedes weight gain and obesity.

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  • Authors+Show Affiliations

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    Center for Behavioral Neuroscience, American University, Washington, DC, United States. Electronic address: terryd@american.edu.

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    Source

    Neuroscience 253: 2013 Dec 03 pg 110-22

    MeSH

    3-Hydroxybutyric Acid
    Adiposity
    Animals
    Blood Glucose
    Body Weight
    Cognition
    Conditioning, Classical
    Diet, Ketogenic
    Discrimination Learning
    Enzyme-Linked Immunosorbent Assay
    Fasting
    Glucagon-Like Peptide 1
    Hippocampus
    Insulin
    Male
    Obesity
    Rats
    Rats, Sprague-Dawley
    Time Factors
    Triglycerides

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    23999121

    Citation

    Davidson, T L., et al. "Inter-relationships Among Diet, Obesity and Hippocampal-dependent Cognitive Function." Neuroscience, vol. 253, 2013, pp. 110-22.
    Davidson TL, Hargrave SL, Swithers SE, et al. Inter-relationships among diet, obesity and hippocampal-dependent cognitive function. Neuroscience. 2013;253:110-22.
    Davidson, T. L., Hargrave, S. L., Swithers, S. E., Sample, C. H., Fu, X., Kinzig, K. P., & Zheng, W. (2013). Inter-relationships among diet, obesity and hippocampal-dependent cognitive function. Neuroscience, 253, pp. 110-22. doi:10.1016/j.neuroscience.2013.08.044.
    Davidson TL, et al. Inter-relationships Among Diet, Obesity and Hippocampal-dependent Cognitive Function. Neuroscience. 2013 Dec 3;253:110-22. PubMed PMID: 23999121.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Inter-relationships among diet, obesity and hippocampal-dependent cognitive function. AU - Davidson,T L, AU - Hargrave,S L, AU - Swithers,S E, AU - Sample,C H, AU - Fu,X, AU - Kinzig,K P, AU - Zheng,W, Y1 - 2013/08/30/ PY - 2013/07/16/received PY - 2013/08/21/revised PY - 2013/08/22/accepted PY - 2013/9/4/entrez PY - 2013/9/4/pubmed PY - 2014/6/20/medline KW - ANOVA KW - BBB KW - BHB KW - DIO KW - DR KW - EDTA KW - FN KW - GLP-1 KW - HE KW - KETO KW - PFC KW - Pavlovian KW - WD KW - Western diet KW - analysis of variance KW - beta-hydroxybutyrate KW - blood–brain barrier KW - dementia KW - diet resistant KW - diet-induced obese KW - energy regulation KW - ethylenediaminetetraacetic acid KW - feature negative KW - glucagon-like peptide-1 KW - high energy KW - ketogenic KW - ketogenic diet KW - memory KW - prefrontal cortex KW - saturated fat SP - 110 EP - 22 JF - Neuroscience JO - Neuroscience VL - 253 N2 - Intake of a Western diet (WD), which is high in saturated fat and sugar, is associated with deficits in hippocampal-dependent learning and memory processes as well as with markers of hippocampal pathology. In the present study, rats were trained to asymptote on hippocampal-dependent serial feature negative (FN) and hippocampal-independent simple discrimination problems. Performance was then assessed following 7 days on ad libitum chow and after 10, 24, 40, 60, and 90 days of maintenance on WD, on ketogenic (KETO) diet, which is high in saturated fat and low in sugar and other carbohydrates, or continued maintenance on chow (CHOW). Confirming and extending previous findings, diet-induced obese (DIO) rats fed WD showed impaired FN performance, increased blood-brain barrier (BBB) permeability, and increased fasting blood glucose levels compared to CHOW controls and to diet-resistant (DR) rats that did not become obese when maintained on WD. For rats fed the KETO diet, FN performance and BBB integrity were more closely associated with level of circulating ketone bodies than with obesity phenotype (DR or DIO), with higher levels of ketones appearing to provide a protective effect. The evidence also indicated that FN deficits preceded and predicted increased body weight and adiposity. This research (a) further substantiates previous findings of WD-induced deficits in hippocampal-dependent FN discriminations, (b) suggests that ketones may be protective against diet-induced cognitive impairment, and (c) provides evidence that diet-induced cognitive impairment precedes weight gain and obesity. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/23999121/Inter_relationships_among_diet_obesity_and_hippocampal_dependent_cognitive_function_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(13)00732-X DB - PRIME DP - Unbound Medicine ER -