Effects of high fat diet on Morris maze performance, oxidative stress, and inflammation in rats: contributions of maternal diet - PubMed (original) (raw)

Effects of high fat diet on Morris maze performance, oxidative stress, and inflammation in rats: contributions of maternal diet

Christy L White et al. Neurobiol Dis. 2009 Jul.

Abstract

This study was undertaken to investigate the effects of prenatal and postnatal exposure to high fat diet on the brain. Female rats were divided into high fat diet (HFD) and control diet (CD) groups 4 weeks prior to breeding and throughout gestation and lactation. After weaning, male progeny were placed on a chow diet until 8 weeks old, and then segregated into HFD or CD groups. At 20 weeks old, rats were evaluated in the Morris water maze, and markers of oxidative stress and inflammation were documented in the brain. In comparison to rats fed CD, cognitive decline in HFD progeny from HFD dams manifested as a decline in retention, but not acquisition, in the water maze. HFD was also associated with significant increases in 3-nitrotyrosine, inducible nitric oxide synthase, IL-6, and glial markers Iba-1 and GFAP, with the largest increases frequently observed in HFD animals born to HFD dams. Thus, these data collectively suggest that HFD increases oxidative and inflammatory signaling in the brain, and further indicate that maternal HFD consumption might sensitize offspring to the detrimental effects of HFD.

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Figures

Figure 1

Figure 1. Effects of maternal and offspring diet on cognitive performance in Morris water maze

Male rats were segregated into 4 groups: CD/CD (rats from CD dams given CD), CD/HFD (rats from CD dams given HFD), HFD/CD (rats from HFD dams given CD), and HFD/HFD (rats from HFD dams given HFD) groups, and the effects of maternal and offspring diet on visuo-spatial learning in 20-week old animals (n = 9-10 per group) was evaluated using the Morris water maze as described in Methods. (A) Mean latency to reach the hidden platform across was measured, and data were analyzed by ANOVA as described in Methods. There was no effect of Maternal Diet or Offspring Diet during acquisition. However, planned comparisons of retention indices (Mean Difference) based on differences in performance between training days as described in Methods indicated that the HFD/HFD group exhibited a significant (p < 0.05) retention deficit compared to the CD/CD group (see graph insert). (B) Mean distance traveled to reach the hidden platform was measured, and data were analyzed by ANOVA. There was no effect of Maternal Diet or Offspring Diet during acquisition. However, planned comparisons of retention indices (Mean Difference) indicated that the HFD/HFD group exhibited a significant (p < 0.05) retention deficit compared to the CD/CD group (see graph insert). (C) Percentage of time spent searching in each quadrant during a 60 sec probe trial was measured, and statistical analyses did not reveal any difference in quadrant preference between the 4 groups.

Figure 2

Figure 2. Effects of maternal and offspring diet on oxidative modifications to proteins in brain

Male rats were segregated into CD/CD, CD/HFD, HFD/CD and HFD/HFD groups as described in Methods, and the effects of maternal and offspring diet on protein carbonylation and nitration in the brains of 20 week old rats was evaluated by dot blot analyses as described in Methods. (A) The accumulation of protein carbonyls in cortical tissue homogenates was measured by evaluating dinitrophenyl (DNP) immunoreactivity levels. Data are means and SEM, with 9-10 individual rats per group, and all samples measured in triplicate. 2-way ANOVA indicated that there was no effect of either Maternal diet or Offspring diet on DNP levels (text insert). (B) The accumulation of 3-nitrotyrosine (3-NT) in cortical tissue homogenates was measured. Data are means and SEM, with 9-10 individual rats per group, with all samples measured in triplicate. 2-way ANOVA indicated an overall significant effect of Offspring Diet on 3-NT levels in the cortex (text insert). (C) Representative low-magnification and high-magnification (insert) images depict the pattern of 3-NT staining in cortex as observed in sections taken at the level of the lateral ventricle.

Figure 3

Figure 3. Effects of maternal and offspring diet on iNOS expression in rat brain

Male rats were segregated into CD/CD, CD/HFD, HFD/CD and HFD/HFD groups as described in Methods, and the effects of maternal and offspring diet on iNOS expression was evaluated by Western blot and immunocytochemistry as described in Methods. (A) The levels of iNOS protein measured by Western blot. Data are means and SEM, with 9-10 individual rats per group, and 2-way ANOVA indicated an overall significant effect of both Maternal diet and Offspring diet on iNOS expression in the cortex (text insert). (B) Representative low-magnification and high-magnification (insert) images depict the pattern of iNOS staining in cortex as observed in sections taken at the level of the lateral ventricle.

Figure 4

Figure 4. Effects of maternal and offspring diet on GFAP expression in rat brain

Male rats were segregated into CD/CD, CD/HFD, HFD/CD and HFD/HFD groups as described in Methods, and the effects of maternal and offspring diet on expression of the astrocyte hypertrophy marker GFAP was evaluated by immunocytochemistry and Western blot as described in Methods. (A) The levels of GFAP protein measured by Western blot. Data are means and SEM, with 9-10 individual rats per group, and 2-way ANOVA indicated an overall significant effect of Offspring diet on GFAP expression in the cortex (text insert). (B) Representative low-magnification and high-magnification (insert) images depict the pattern of GFAP staining in cortex as observed in sections taken at the level of the lateral ventricle.

Figure 5

Figure 5. Effects of maternal and offspring diet on Iba-1 expression in rat brain

Male rats were segregated into CD/CD, CD/HFD, HFD/CD and HFD/HFD groups as described in Methods, and the effects of maternal and offspring diet on expression of the microglia marker Iba-1 was evaluated by immunocytochemistry and Western blot as described in Methods. (A) The levels of Iba-1 protein measured by Western blot. Data are means and SEM, with 9-10 individual rats per group, and ANOVA indicated an overall significant effect of Offspring diet on Iba-1 expression in the cortex (text insert). (B) Representative low-magnification and high-magnification (insert) images depict the pattern of Iba-1 staining in cortex as observed in sections taken at the level of the lateral ventricle.

Figure 6

Figure 6. Effects of maternal and offspring diet on cytokine levels in rat brain

Male rats were segregated into CD/CD, CD/HFD, HFD/CD and HFD/HFD groups as described in Methods, and the effects of maternal and offspring diet on cytokine expression in the brains of 20 week old rats was evaluated by ELISA as described in Methods. (A) TNFα levels in cortical homogenates were measured. Data are means and SEM, with 9-10 individual rats per group, and 2-way ANOVA indicated that there was no effect of either Maternal diet or Offspring diet on TNF expression (text insert). (B) Expression of IL-6 in the cortex of rats was measured by ELISA. Data are means and SEM, with 9-10 individual rats per group, and 2-way ANOVA indicated an overall significant effect of Maternal diet on IL-6 expression in the cortex (text insert).

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