Hypercholesterolemia and neurodegeneration. Comparison of hippocampal phenotypes in LDLr knockout and APPswe/PS1dE9 mice

Ettcheto, Miren; Петров, Д. С.; Pedrós, Ignacio; Lemos, Luisa de; Pallàs, Mercè; Alegret, Marta; Laguna, Juan C.; Folch, Jaume; Camins, Antoni

doi:10.1016/j.exger.2015.03.010

Cited by 21 publications

(28 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, highcholesterol diet-treated mice exhibited cognitive dysfunction in the Morris water maze test (27). Ettcheto et al described the relationship between hypercholesterolemia and neurodegeneration using low density lipoprotein (LDL) receptor knockout and amyloid precursor protein (APP)/presenilin (PS) 1 transgenic mice (28). Treatment with a-tocopherol attenuated high-cholesterol diet-induced elevation of serum cholesterol level in rabbit models (29).…”

Section: The Possible Role Of Vitamin E Deficiency-induced Elevated Smentioning

confidence: 99%

Long-Term Vitamin E-Deficient Mice Exhibit Cognitive Dysfunction via Elevation of Brain Oxidation

Fukui

Nakamura

Shirai

et al. 2015

J Nutr Sci Vitaminol

View full text Add to dashboard Cite

Summary Vitamin E inhibits oxidative processes in living tissues. We produced vitamin E-deficient mice by feeding them a vitamin E-deficient diet to verify the influence of chronic vitamin E deficiency on cognitive function. We measured cognitive function over a 5-d period using the Morris water maze task, as well as antioxidant enzyme activity and lipid peroxidation in discrete brain regions, and total serum cholesterol content. Threeand six-mo-old vitamin E-deficient and age-matched control mice were used. In addition, 24-mo-old mice were used as an aged-model. In the 3-mo-old mice, cognitive function in the vitamin E-deficient (short-term vitamin E-deficient) group was significantly impaired compared to age-matched controls. Although the lipid peroxidation products in the cerebral cortex, cerebellum and hippocampus did not significantly differ in 3-mo-old mice, the levels in the 6-mo-old vitamin E-deficient (long-term vitamin E-deficient) mice were significantly increased compared to age-matched controls. Serum cholesterol content was also significantly increased in the short-and long-term vitamin E-deficient mice compared to their respective age-matched controls. These results indicate that chronic vitamin E deficiency may slowly accelerate brain oxidation. Thus, vitamin E concentrations may need to be monitored in order to prevent the risk of cognitive dysfunction, even under normal conditions.

show abstract

Section: The Possible Role Of Vitamin E Deficiency-induced Elevated Smentioning

confidence: 99%

Long-Term Vitamin E-Deficient Mice Exhibit Cognitive Dysfunction via Elevation of Brain Oxidation

Fukui

Nakamura

Shirai

et al. 2015

J Nutr Sci Vitaminol

View full text Add to dashboard Cite

show abstract

“…As expected, analysis of the lipidic parameter for the HD group revealed a significant modification of the plasma lipidic profile, with an increase of 1000% in LDL-C, 400% in TC, and 130% in TG levels. Many epidemiological (27) and in vivo studies using wild type and transgenic animals such as mice (1,(28)(29)(30) have supported a strong association between the pathogenesis of AD and circulating LDL-C. Chen et al have shown that increased levels of LDL-C can lead to disturbances in the endolysosome structure in neurons and, following APP internalization, can promote the accumulation of Aβ deposits (31). In our experiment, despite an approximately fourfold increase in TC plasma levels, we observed no marked change in brain TC.…”

Section: Discussionmentioning

confidence: 99%

“…mice that were fed with a high-cholesterol diet (1). Many studies have demonstrated that the LDLr mice exhibit cognitive impairment and irregularities in the MWM test (1,36).…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have demonstrated that the LDLr mice exhibit cognitive impairment and irregularities in the MWM test (1,36). In addition, recent studies have demonstrated an association between the severity of cognitive impairment and elevated levels of cholesterol (29).…”

Section: Discussionmentioning

confidence: 99%

“…Despite restrictions to the entrance of LDL, the main transporter of cholesterol in plasma from the blood brain barrier (BBB) to the brain parenchyma (2), an association between elevated levels of plasma cholesterol and the risk of dementia or other cognition-related diseases (3) has been demonstrated frequently (1,4).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

High Cholesterol Diet Increases Expression of Cholesterol 24-Hydroxylase and BACE1 in Rat Hippocampi: Implications for the Effect of Diet Cholesterol on Memory

Nikasa¹,

Karimi²,

Rajavand³

et al. 2016

Iran Red Crescent Med J

View full text Add to dashboard Cite

Background: Abnormal cholesterol homeostasis is associated with the pathogenesis of neurodegenerative disease and cognitive impairment. Objectives: Our objective was to evaluate changes in the expression of proteins related to cognition and cholesterol homeostasis in the hippocampi of rats as well as behavioral modifications following the administration of a cholesterol-rich diet. Methods: In this experimental study, lasting 16 weeks, 20 male Wistar rats (aged 8 weeks) were randomly divided into two groups. One group was fed with a normal diet (ND; n = 10) and the second with a high cholesterol diet (HD; n = 10). The expression of the cognition-related proteins N-methyl-D-aspartate receptor (NMDAR) and beta-secretase 1 (BACE1) and cholesterol 24-hydroxylase (CYP46A1), the key cholesterol hemostasis protein, were determined by an immunoblotting assay in the hippocampus homogenate. The Morris water maze (MWM) test was used to examine cognitive performance. Plasma lipidic parameters, including total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG), as well as brain TC were measured by colorimetric assay. Results: After a high cholesterol diet had been administered for a period of 16 weeks, a significant increase in TC, LDL-C and TG was observed in the HD group in comparison with the ND group (P < 0.05). Neither the mean of brain wet weight nor brain TC showed significant change in the HD versus the ND group (P = 0.114, P = 0.84, respectively). Despite this fixity, differences in the expression of BACE1 and CYP46A1 were significant (P < 0.05) between the two groups, with high levels of BACE1 and CYP46A1 in the HD group compared with the ND group. These biochemical changes were associated with a significant decrease in the time traveled on a platform quadrant in the HD versus the ND group (P < 0.05) during a spatial memory probe test administered at the same time. Conclusions:The findings show that irregularities in cognitive performance as a result of a high cholesterol diet can be partially mediated by distortion in brain cholesterol homeostasis and processing of the amyloid precursor protein (APP).

show abstract

MALDI-Mass Spectrometry Imaging to Investigate Lipid and Bile Acid Modifications Caused by Lentil Extract Used as a Potential Hypocholesterolemic Treatment

Genangeli

Heijens

Rustichelli

et al. 2019

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

This paper reports matrix-assisted laser desorption/ionization mass spectrometry imaging to investigate systematic effects of a lentil extract treatment to lower cholesterol levels. For this purpose, mass spectrometry imaging was used to spatially investigate modifications in the lipid composition and cholesterol levels in the brain, liver, and intestines as well as bile acids in the liver and intestine of rats treated with lentil extract. Neither the lipid composition nor cholesterol levels in the brain samples were found to be significantly different between the treated and not-treated animal groups. The hypercholesterolemic livers showed signs of steatosis (lipid marker PG 36:4), but no modifications in bile acid, cholesterol, and lipid composition. We found significant differences (AUC > 0.75) in the intestines regarding bile acid and lipid composition after treatment with the lentil extract. The treated rats showed a decreased reabsorption (increased excretion) of ursodeoxycholic acid, deoxycholic acid, and chenodeoxycholic acid and an increased deconjugation of taurine-conjugated bile acids (taurochenodeoxycholic acid, taurodeoxycholic acid, taurocholic acid, and 3-keto-taurocholic acid). This indicates that the lentil extract lowers the total cholesterol level in two synergic ways: (i) it increases the excretion of bile acids; hence, new bile acids are produced in the liver from serum cholesterol and (ii) the prebiotic effect leads to free taurine which upregulates the de novo synthesis of bile acid from cholesterol while activating LDL receptors. We demonstrate here that mass spectrometry imaging is a valuable tool for a better understanding of the effects of treatments such as for the synergistic cholesterol-lowering effect of the lentil extract. Electronic supplementary materialThe online version of this article (10.1007/s13361-019-02265-9) contains supplementary material, which is available to authorized users.

show abstract

Hypercholesterolemia and neurodegeneration. Comparison of hippocampal phenotypes in LDLr knockout and APPswe/PS1dE9 mice

Cited by 21 publications

References 67 publications

Long-Term Vitamin E-Deficient Mice Exhibit Cognitive Dysfunction via Elevation of Brain Oxidation

Long-Term Vitamin E-Deficient Mice Exhibit Cognitive Dysfunction via Elevation of Brain Oxidation

High Cholesterol Diet Increases Expression of Cholesterol 24-Hydroxylase and BACE1 in Rat Hippocampi: Implications for the Effect of Diet Cholesterol on Memory

MALDI-Mass Spectrometry Imaging to Investigate Lipid and Bile Acid Modifications Caused by Lentil Extract Used as a Potential Hypocholesterolemic Treatment

Contact Info

Product

Resources

About