Iranian Red Crescent Medical Journal

Published by: Kowsar

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

Mitra Nikasa 1 , Pouran Karimi 2 , * , Hosnieh Rajavand 1 , Fatemeh Afshari 3 , Mahdi Jafarlou 4 and Mahboob Soltanali 1
Authors Information
1 Higher Academic Education Institute of Rabe Rashid, Tabriz, IR Iran
2 Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, IR Iran
3 Department of Histopathology, Tabriz Medical Sciences Branch, Islamic Azad University, Tabriz, IR Iran
4 Faculty of Medicine and Health Sciences, UPM, Serdang, Malaysia
Article information
  • Iranian Red Crescent Medical Journal: December 01, 2016, 18 (12); e35677
  • Published Online: August 30, 2016
  • Article Type: Research Article
  • Received: January 3, 2016
  • Revised: February 8, 2016
  • Accepted: April 23, 2016
  • DOI: 10.5812/ircmj.35677

To Cite: Nikasa M, Karimi P, Rajavand H, Afshari F, Jafarlou M, et al. High Cholesterol Diet Increases Expression of Cholesterol 24-Hydroxylase and BACE1 in Rat Hippocampi: Implications for the Effect of Diet Cholesterol on Memory, Iran Red Crescent Med J. 2016 ; 18(12):e35677. doi: 10.5812/ircmj.35677.

Copyright © 2016, Iranian Red Crescent Medical Journal. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background
2. Objectives
3. Methods
4. Results
5. Discussion
  • 1. Ettcheto M, Petrov D, Pedros I, de Lemos L, Pallas M, Alegret M, et al. Hypercholesterolemia and neurodegeneration. Comparison of hippocampal phenotypes in LDLr knockout and APPswe/PS1dE9 mice. Exp Gerontol. 2015; 65: 69-78[DOI][PubMed]
  • 2. Iuliano L, Crick PJ, Zerbinati C, Tritapepe L, Abdel-Khalik J, Poirot M, et al. Cholesterol metabolites exported from human brain. Steroids. 2015; 99: 189-93[DOI][PubMed]
  • 3. Picco R, Tomasella A, Fogolari F, Brancolini C. Transcriptomic analysis unveils correlations between regulative apoptotic caspases and genes of cholesterol homeostasis in human brain. PLoS One. 2014; 9(10): 110610[DOI][PubMed]
  • 4. Irizarry MC. Biomarkers of Alzheimer disease in plasma. NeuroRx. 2004; 1(2): 226-34[DOI][PubMed]
  • 5. Bjorkhem I, Meaney S. Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol. 2004; 24(5): 806-15[DOI][PubMed]
  • 6. Valdez CM, Phelix CF, Smith MA, Perry G, Santamaria F. Modeling cholesterol metabolism by gene expression profiling in the hippocampus. Mol Biosyst. 2011; 7(6): 1891-901[DOI][PubMed]
  • 7. Ramirez DM, Andersson S, Russell DW. Neuronal expression and subcellular localization of cholesterol 24-hydroxylase in the mouse brain. J Comp Neurol. 2008; 507(5): 1676-93[DOI][PubMed]
  • 8. Vega GL, Weiner MF, Lipton AM, Von Bergmann K, Lutjohann D, Moore C, et al. Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease. Arch Neurol. 2003; 60(4): 510-5[DOI][PubMed]
  • 9. Murr J, Carmichael PH, Julien P, Laurin D. Plasma oxidized low-density lipoprotein levels and risk of Alzheimer's disease. Neurobiol Aging. 2014; 35(8): 1833-8[DOI][PubMed]
  • 10. Hughes TM, Rosano C, Evans RW, Kuller LH. Brain cholesterol metabolism, oxysterols, and dementia. J Alzheimers Dis. 2013; 33(4): 891-911[DOI][PubMed]
  • 11. Milagre I, Olin M, Nunes MJ, Moutinho M, Lovgren-Sandblom A, Gama MJ, et al. Marked change in the balance between CYP27A1 and CYP46A1 mediated elimination of cholesterol during differentiation of human neuronal cells. Neurochem Int. 2012; 60(2): 192-8[DOI][PubMed]
  • 12. Marwarha G, Ghribi O. Does the oxysterol 27-hydroxycholesterol underlie Alzheimer's disease-Parkinson's disease overlap? Exp Gerontol. 2015; 68: 13-8[DOI][PubMed]
  • 13. Burlot MA, Braudeau J, Michaelsen-Preusse K, Potier B, Ayciriex S, Varin J, et al. Cholesterol 24-hydroxylase defect is implicated in memory impairments associated with Alzheimer-like Tau pathology. Hum Mol Genet. 2015; 24(21): 5965-76[DOI][PubMed]
  • 14. Kuo PH, Lin CI, Chen YH, Chiu WC, Lin SH. A high-cholesterol diet enriched with polyphenols from Oriental plums (Prunus salicina) improves cognitive function and lowers brain cholesterol levels and neurodegenerative-related protein expression in mice. Br J Nutr. 2015; 113(10): 1550-7[DOI][PubMed]
  • 15. Paul SM, Doherty JJ, Robichaud AJ, Belfort GM, Chow BY, Hammond RS, et al. The major brain cholesterol metabolite 24(S)-hydroxycholesterol is a potent allosteric modulator of N-methyl-D-aspartate receptors. J Neurosci. 2013; 33(44): 17290-300[DOI][PubMed]
  • 16. Fenik VB, Kubin L. Differential localization of carbachol- and bicuculline-sensitive pontine sites for eliciting REM sleep-like effects in anesthetized rats. J Sleep Res. 2009; 18(1): 99-112[DOI][PubMed]
  • 17. Abo El-Khair DM, El-Safti Fel N, Nooh HZ, El-Mehi AE. A comparative study on the effect of high cholesterol diet on the hippocampal CA1 area of adult and aged rats. Anat Cell Biol. 2014; 47(2): 117-26[DOI][PubMed]
  • 18. Sanbe T, Tomofuji T, Ekuni D, Azuma T, Irie K, Tamaki N, et al. Vitamin C intake inhibits serum lipid peroxidation and osteoclast differentiation on alveolar bone in rats fed on a high-cholesterol diet. Arch Oral Biol. 2009; 54(3): 235-40[DOI][PubMed]
  • 19. Ramakrishnan SK, Khuder SS, Al-Share QY, Russo L, Abdallah SL, Patel PR, et al. PPARalpha (Peroxisome Proliferator-activated Receptor alpha) Activation Reduces Hepatic CEACAM1 Protein Expression to Regulate Fatty Acid Oxidation during Fasting-refeeding Transition. J Biol Chem. 2016; 291(15): 8121-9[DOI][PubMed]
  • 20. Verreth W, De Keyzer D, Pelat M, Verhamme P, Ganame J, Bielicki JK, et al. Weight-loss-associated induction of peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gamma correlate with reduced atherosclerosis and improved cardiovascular function in obese insulin-resistant mice. Circulation. 2004; 110(20): 3259-69[DOI][PubMed]
  • 21. Underwood EL, Thompson LT. High-fat diet impairs spatial memory and hippocampal intrinsic excitability and sex-dependently alters circulating insulin and hippocampal insulin sensitivity. Biol Sex Differ. 2016; 7: 9[DOI][PubMed]
  • 22. Kann O. The interneuron energy hypothesis: Implications for brain disease. Neurobiol Dis. 2016; 90: 75-85[DOI][PubMed]
  • 23. Casali BT, Corona AW, Mariani MM, Karlo JC, Ghosal K, Landreth GE. Omega-3 Fatty Acids Augment the Actions of Nuclear Receptor Agonists in a Mouse Model of Alzheimer's Disease. J Neurosci. 2015; 35(24): 9173-81[DOI][PubMed]
  • 24. Au A, Feher A, McPhee L, Jessa A, Oh S, Einstein G. Estrogens, inflammation and cognition. Front Neuroendocrinol. 2016; 40: 87-100[DOI][PubMed]
  • 25. Kruk-Slomka M, Boguszewska-Czubara A, Slomka T, Budzynska B, Biala G. Correlations between the Memory-Related Behavior and the Level of Oxidative Stress Biomarkers in the Mice Brain, Provoked by an Acute Administration of CB Receptor Ligands. Neural Plast. 2016; 2016: 9815092[DOI][PubMed]
  • 26. Klosinski LP, Yao J, Yin F, Fonteh AN, Harrington MG, Christensen TA, et al. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease. EBioMedicine. 2015; 2(12): 1888-904[DOI][PubMed]
  • 27. Tan ZS, Seshadri S, Beiser A, Wilson PW, Kiel DP, Tocco M, et al. Plasma total cholesterol level as a risk factor for Alzheimer disease: the Framingham Study. Arch Intern Med. 2003; 163(9): 1053-7[DOI][PubMed]
  • 28. Lutjohann D, Stroick M, Bertsch T, Kuhl S, Lindenthal B, Thelen K, et al. High doses of simvastatin, pravastatin, and cholesterol reduce brain cholesterol synthesis in guinea pigs. Steroids. 2004; 69(6): 431-8[DOI][PubMed]
  • 29. Prasanthi JR, Larson T, Schommer J, Ghribi O. Silencing GADD153/CHOP gene expression protects against Alzheimer's disease-like pathology induced by 27-hydroxycholesterol in rabbit hippocampus. PLoS One. 2011; 6(10): 26420[DOI][PubMed]
  • 30. Mast N, Reem R, Bederman I, Huang S, DiPatre PL, Bjorkhem I, et al. Cholestenoic Acid is an important elimination product of cholesterol in the retina: comparison of retinal cholesterol metabolism with that in the brain. Invest Ophthalmol Vis Sci. 2011; 52(1): 594-603[DOI][PubMed]
  • 31. Chen YL, Wang LM, Chen Y, Gao JY, Marshall C, Cai ZY, et al. Changes in astrocyte functional markers and beta-amyloid metabolism-related proteins in the early stages of hypercholesterolemia. Neuroscience. 2016; 316: 178-91[DOI][PubMed]
  • 32. Sun MY, Izumi Y, Benz A, Zorumski CF, Mennerick S. Endogenous 24S-hydroxycholesterol modulates NMDAR-mediated function in hippocampal slices. J Neurophysiol. 2016; 115(3): 1263-72[DOI][PubMed]
  • 33. Noguchi N, Saito Y, Urano Y. Diverse functions of 24(S)-hydroxycholesterol in the brain. Biochem Biophys Res Commun. 2014; 446(3): 692-6[DOI][PubMed]
  • 34. Mehra R, Sodhi RK, Aggarwal N. Memory restorative ability of clioquinol in copper-cholesterol-induced experimental dementia in mice. Pharm Biol. 2015; 53(9): 1250-9[DOI][PubMed]
  • 35. Li M, Wang W, Li Y, Wang L, Shen X, Tang Z. CYP46A1 intron-2T/C polymorphism and Alzheimer's disease: an updated meta-analysis of 16 studies including 3,960 cases and 3,828 controls. Neurosci Lett. 2013; 549: 18-23[DOI][PubMed]
  • 36. Ghribi O, Larsen B, Schrag M, Herman MM. High cholesterol content in neurons increases BACE, beta-amyloid, and phosphorylated tau levels in rabbit hippocampus. Exp Neurol. 2006; 200(2): 460-7[DOI][PubMed]
  • 37. Noguchi N, Urano Y, Takabe W, Saito Y. New aspects of 24(S)-hydroxycholesterol in modulating neuronal cell death. Free Radic Biol Med. 2015; 87: 366-72[DOI][PubMed]
  • 38. Wang H, Ardiles AO, Yang S, Tran T, Posada-Duque R, Valdivia G, et al. Metabotropic Glutamate Receptors Induce a Form of LTP Controlled by Translation and Arc Signaling in the Hippocampus. J Neurosci. 2016; 36(5): 1723-9[DOI][PubMed]
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