Inter-relationships among diet, obesity and hippocampal-dependent cognitive function - PubMed (original) (raw)

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

T L Davidson et al. Neuroscience. 2013.

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.

Keywords: ANOVA; BBB; BHB; DIO; DR; EDTA; FN; GLP-1; HE; KETO; PFC; Pavlovian; WD; Western diet; analysis of variance; beta-hydroxybutyrate; blood–brain barrier; dementia; diet resistant; diet-induced obese; energy regulation; ethylenediaminetetraacetic acid; feature negative; glucagon-like peptide-1; high energy; ketogenic; ketogenic diet; memory; prefrontal cortex; saturated fat.

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Figures

Figure 1

Mean body weight (g) for rats fed WD (WD-DR and WD-DIO), ketogenic diet (KETO-DR and KETO-DIO), or standard chow (CHOW-DR and CHOW-DIO) at baseline and throughout the 90-day diet exposure. Alphabetic indicators (a, b, c, d,) shown in the legend are used to denote groups that differed significantly (ps < .05) from CHOW-DIO and CHOW-DR groups on a given probe test day. Differences between CHOW-DIO and CHOW-DR groups were not significant on any day of probe testing. Vertical bars depict standard error of the mean (SEM).

Figure 2

Mean percent body fat for rats fed WD (WD-DR and WD-DIO), ketogenic diet (KETO-DR and KETO-DIO), or standard chow (CHOW-DR and CHOW-DIO) at baseline and throughout the 90-day diet exposure. Alphabetic indicators (a, b, c, d,) shown in the legend are used to denote groups that differed significantly (ps < .05) from CHOW-DIO and CHOW-DR groups on a given probe test day. Differences between CHOW-DIO and CHOW-DR groups were not significant on any day of probe testing. Vertical bars depict standard error of the mean (SEM).

Figure 3

Simple (CS+ and CS−; top panels) and serial FN (T+, L→ T− ; bottom panels) discrimination performance, as indexed by mean beam breaks, on the last 2 blocks of training when food deprived (Train), after 7 days on ad lib standard chow (BL), and 10, 24, 40, 60, and 90 days after the introduction of WD (WD-DR and WD-DIO), ketogenic diet (KETO-DR and KETO-DIO), or continuation on standard chow (CHOW). * denote probe tests in which responding on rewarded trials was significantly greater than on nonrewarded trials. Brackets with a corresponding * denote contiguous probe test days in which the difference in responding on rewarded compared to nonrewarded trials was significant. Error bars depict SEM.

Figure 4

Mean beta-hydroxybutyrate levels for rats fed WD (WD-DR and WD-DIO), ketogenic diet (KETO-DR and KETO-DIO), or standard chow (CHOW) at baseline when all groups were fed ad libitum standard chow and on each probe test day (10, 24, 40, 60 and 90) after the experimental diets were introduced. Alphabetic indicators (a, b, c, d,) shown in the legend are used to denote groups that differed significantly (ps < .05) from CHOW controls on a given test day. Error bars depict SEM.

Figure 5

Mean triglyceride levels for rats fed WD (WD-DR and WD-DIO), ketogenic diet (KETO-DR and KETO-DIO), or standard chow (CHOW) at baseline test when all groups were fed ad libitum standard chow and on each probe test day (10, 24, 40, 60 and 90) after the experimental diets were introduced. Alphabetic indicators (a, b, c, d,) shown in the legend are used to denote groups that differed significantly (ps < .05) from CHOW controls on a given test day. No significant differences were observed on any test. Error bars depict SEM.

Figure 6

NaFl concentration (μg NaFl/mg brain tissue), a measure of BBB permeability, in hippocampus, striatum, PFC, and cerebellum for rats maintained on WD (WD-DIO and WD-DR), ketogenic diet (KETO-DIO), and standard chow (CHOW) for 90 days. * denote significant difference (p < .05) from CHOW control. Error bars depict SEM.

Figure 7

Cross-lagged panel correlations depicting the correlations the degree and direction of relationship between FN discrimination performance and ketone levels (top two panels), body weight (middle two panels), and percent body fat (bottom two panels) on probes test days 24 and 90 for rats fed WD- (left panels) and KETO diet (right panels), respectively. Significant correlations (ps < 05) are indicated by numbers that are in italicized, bold-face font, with an accompanying *.

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Inter-relationships among diet, obesity and hippocampal-dependent cognitive function - PubMed (original) (raw)