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Drug Res (Stuttg) 2015; 65(05): 231-237
DOI: 10.1055/s-0034-1370950
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Investigation of the Memory Impairment in Rats Fed with Oxidized-Cholesterol-Rich Diet Employing Passive Avoidance Test

A. Khorrami
1   Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
2   Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
4   Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
S. Ghanbarzadeh
2   Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
3   Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
4   Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
J. Mahmoudi
1   Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
A. M. Nayebi
1   Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
N. Maleki-Dizaji
1   Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
A. Garjani
1   Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
› Author Affiliations
Further Information

Publication History

received 11 December 2013

accepted 13 February 2014

Publication Date:
25 March 2014 (online)

Also available at
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Abstract

Background:

Recent studies have shown that hypercholesterolemia, besides being a risk factor for cardiovascular diseases, has also toxic effects on central nervous system. The design of the present study was to investigate the effects of dietary cholesterol and oxidized cholesterol on cognitive function.

Methods:

Male Wistar rats were randomly divided into 3 groups. The animals were fed with three normal, 2% cholesterol-rich, and 2% oxidized cholesterol-rich diets for 14 weeks. Memory impairment was analyzed by passive avoidance test. Coenzyme Q10 content was also measured by a validate RP-HPLC method. Besides, lipid peroxidation in serum and brain tissue was determined by malondialdehyde concentration measurement.

Results:

The results showed that feeding rats with high oxidized cholesterol diet for 14 weeks significantly impaired the cognitive function compared to the normal (P<0.001) and high cholesterol-fed groups (P<0.01). The memory impairment was positively correlated to the serum level of the oxidized LDL; it was significantly associated with the increased malondialdehyde concentration on the brain tissue of both groups (P<0.05 and P<0.001, respectively). The total antioxidant level in the serum was also decreased in rats fed with the oxidized cholesterol (P<0.05). Moreover, the brain coenzyme Q10 content was significantly declined in the animals fed with the oxidized cholesterol-rich diet compared to the animals fed with the normal (P<0.01) and cholesterol-rich diets (P<0.05).

Conclusion:

The results suggested that the high dietary intake of the oxidized-cholesterol might impair the memory that could be correlated to the oxidative stress and declined the coenzyme Q10 content of the brain tissue.

Key words

cholesterol - oxidized cholesterol - coenzyme Q10 - memory impairment
 

  • References

  • 1 Bäckman L, Small BJ. Cognitive deficits in preclinical Alzheimer’s disease and vascular dementia: Patterns of findings from the Kungsholmen Project. Physiology & Behavior 2007; 92: 80-86
    CrossrefPubMedGoogle Scholar
  • 2 Ishrat T, Parveen K, Khan MM et al. Selenium prevents cognitive decline and oxidative damage in rat model of streptozotocin-induced experimental dementia of Alzheimer’s type. Brain Research 2009; 1281: 117-127
    CrossrefPubMedGoogle Scholar
  • 3 Stopford CL, Thompson JC, Neary D et al. Working memory, attention, and executive function in Alzheimer’s disease and frontotemporal dementia. Cortex 2012; 48: 429-446
    CrossrefPubMedGoogle Scholar
  • 4 Kerola T, Kettunen R, Nieminen T. The complex interplay of cardiovascular system and cognition: How to predict dementia in the elderly?. International Journal of Cardiology 2011; 150: 123-129
    CrossrefPubMedGoogle Scholar
  • 5 Kling MA, Trojanowski JQ, Wolk DA et al. Vascular disease and dementias: Paradigm shifts to drive research in new directions. Alzheimer’s & Dementia 2013; 9: 76-92
    CrossrefPubMedGoogle Scholar
  • 6 Mattson MP. Roles of the lipid peroxidation product 4-hydroxynonenal in obesity, the metabolic syndrome, and associated vascular and neurodegenerative disorders. Experimental Gerontology 2009; 44: 625-633
    CrossrefPubMedGoogle Scholar
  • 7 Castello MA, Soriano S. Rational heterodoxy: Cholesterol reformation of the amyloid doctrine. Ageing Research Reviews 2013; 12: 282-288
    CrossrefPubMedGoogle Scholar
  • 8 Liu J-P, Tang Y, Zhou S et al. Cholesterol involvement in the pathogenesis of neurodegenerative diseases. Molecular and Cellular Neuroscience 2010; 43: 33-42
    CrossrefPubMedGoogle Scholar
  • 9 Mathew A, Yoshida Y, Maekawa T et al. Alzheimer’s disease: Cholesterol a menace?. Brain Research Bulletin 2011; 86: 1-12
    CrossrefPubMedGoogle Scholar
  • 10 Khorrami A, Ghanbarzadeh S, Ziaee M et al. Effects of LDL and Oxidized LDL on Cardiac Function in Isoproterenol-induced Myocardial Infarction in Rat. Drug Research 2014; In Press
    PubMedGoogle Scholar
  • 11 Wolozin B, Kellman W, Ruosseau P et al. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000; 57: 1439-1443
    CrossrefPubMedGoogle Scholar
  • 12 Almuti K, Rimawi R, Spevack D et al. Effects of statins beyond lipid lowering: Potential for clinical benefits. International Journal of Cardiology 2006; 109: 7-15
    CrossrefPubMedGoogle Scholar
  • 13 DeKosky ST. Statin therapy in the treatment of Alzheimer disease: what is the rationale?. The American Journal of Medicine 2005; 118: 48-53
    CrossrefPubMedGoogle Scholar
  • 14 Green RC, McNagny SE, Jayakumar P et al. Statin use and the risk of Alzheimer’s disease: The MIRAGE Study. Alzheimer’s & Dementia 2006; 2: 96-103
    CrossrefPubMedGoogle Scholar
  • 15 Björkhem I. Five decades with oxysterols. Biochimie 2013; 95: 448-454
    CrossrefPubMedGoogle Scholar
  • 16 Gosselet F, Saint-Pol J, Fenart L. Effects of oxysterols on the blood–brain barrier: Implications for Alzheimer’s disease. Biochemical and Biophysical Research Communications 2013; In press: In press
    PubMedGoogle Scholar
  • 17 Leoni V, Caccia C. Oxysterols as biomarkers in neurodegenerative diseases. Chemistry and Physics of Lipids 2011; 164: 515-524
    CrossrefPubMedGoogle Scholar
  • 18 Block RC, Dorsey ER, Beck CA et al. Altered cholesterol and fatty acid metabolism in Huntington disease. Journal of Clinical Lipidology 2010; 4: 17-23
    CrossrefPubMedGoogle Scholar
  • 19 Leoni V, Caccia C. 24S-hydroxycholesterol in plasma: A marker of cholesterol turnover in neurodegenerative diseases. Biochimie 2013; 95: 595-612
    CrossrefPubMedGoogle Scholar
  • 20 Pfrieger FW, Ungerer N. Cholesterol metabolism in neurons and astrocytes. Progress in Lipid Research 2011; 50: 357-371
    CrossrefPubMedGoogle Scholar
  • 21 Quan G, Xie C, Dietschy JM et al. Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse. Developmental Brain Research 2003; 146: 87-98
    CrossrefPubMedGoogle Scholar
  • 22 Schreurs BG. The effects of cholesterol on learning and memory. Neuroscience & Biobehavioral Reviews 2010; 34: 1366-1379
    CrossrefPubMedGoogle Scholar
  • 23 Valenza M, Cattaneo E. Emerging roles for cholesterol in Huntington’s disease. Trends in Neurosciences 2011; 34: 474-486
    CrossrefPubMedGoogle Scholar
  • 24 Andersson M, Elmberger PO, Edlund C et al. Rates of cholesterol, ubiquinone, dolichol and dolichyl-P biosynthesis in rat brain slices. FEBS Letters 1990; 269: 15-18
    CrossrefPubMedGoogle Scholar
  • 25 Thelen KM, Falkai P, Bayer TA et al. Cholesterol synthesis rate in human hippocampus declines with aging. Neuroscience Letters 2006; 403: 15-19
    CrossrefPubMedGoogle Scholar
  • 26 Leoni V, Masterman T, Patel P et al. Side chain oxidized oxysterols in cerebrospinal fluid and the integrity of blood-brain and bloodcerebrospinal fluid barriers. Journal of Lipid Research 2003; 44: 793-799
    CrossrefPubMedGoogle Scholar
  • 27 Cartagena CM, Burns MP, Rebeck GW. 24S-hydroxycholesterol effects on lipid metabolism genes are modeled in traumatic brain injury. Brain Research 2010; 1319: 1-12
    CrossrefPubMedGoogle Scholar
  • 28 Lütjohann D, Breuer O, Ahlborg G et al. Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. Proc Natl Acad Sci USA 1996; 93: 9799-9804
    CrossrefPubMedGoogle Scholar
  • 29 Nilsen J. Estradiol and neurodegenerative oxidative stress. Frontiers in Neuroendocrinology 2008; 29: 463-475
    CrossrefPubMedGoogle Scholar
  • 30 Yan MH, Wang X, Zhu X. Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease. Free Radical Biology and Medicine 2013; 62: 90-101
    CrossrefPubMedGoogle Scholar
  • 31 Ghanbarzadeh S, Garjani A, Ziaee M et al. CoQ10 and L-Carnitine Attenuate the Effect of High LDL and Oxidized LDL on Spermatogenesis in Male Rats. Drug Research 2014; In Press
    PubMedGoogle Scholar
  • 32 Choi H, Park H-H, Koh S-H et al. Coenzyme Q10 protects against amyloid beta-induced neuronal cell death by inhibiting oxidative stress and activating the P13K pathway. NeuroToxicology 2012; 33: 85-90
    CrossrefPubMedGoogle Scholar
  • 33 Somayajulu M, McCarthy S, Hung M et al. Role of mitochondria in neuronal cell death induced by oxidative stress; neuroprotection by Coenzyme Q10. Neurobiology of Disease 2005; 18: 618-627
    CrossrefPubMedGoogle Scholar
  • 34 Ghanbarzadeh S, Garjani A, Ziaee M et al. Effects of L-Carnitine and Coenzyme Q10 on Impaired Spermatogenesis Caused by Isoproterenol in Male Rats. Drug Research 2014; In Press
    PubMedGoogle Scholar
  • 35 Kamat SM, Kamat AS, Grossberg GT. Dementia Risk Prediction: Are We There Yet?. Clinics in Geriatric Medicine 2010; 26: 113-123
    CrossrefPubMedGoogle Scholar
  • 36 Patterson C, Feightner J, Garcia A et al. Primary prevention of dementia. Alzheimer’s & Dementia 2007; 3: 348-354
    CrossrefPubMedGoogle Scholar
  • 37 Staprans I, Pan XM, Rapp JH et al. Oxidized Cholesterol in the Diet Accelerates the Development of Atherosclerosis in LDLReceptor – and Apolipoprotein E-Deficient Mice Arterioscler. Thromb Vasc Biol 2000; 20: 708-714
    CrossrefPubMedGoogle Scholar
  • 38 Satoh K. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta 1978; 90: 37-43
    CrossrefPubMedGoogle Scholar
  • 39 Khorrami A, Ghanbarzadeh S, garjani A et al. Reduction of Coenzyme Q10 Content: A Possible Effect of Isoproterenol on Heart Failure and Myocardial Infarction in Rat. Drug Research 2014; In Press
    PubMedGoogle Scholar
  • 40 Waseem TV, Kolos VA, Lapatsina LP et al. Influence of cholesterol depletion in plasma membrane of rat brain synaptosomes on calcium-dependent and calcium-independent exocytosis. Neuroscience Letters 2006; 405: 106-110
    CrossrefPubMedGoogle Scholar
  • 41 Pensalfini A, Zampagni M, Liguri G et al. Membrane cholesterol enrichment prevents Aβ-induced oxidative stress in Alzheimer’s fibroblasts. Neurobiology of Aging 2011; 32: 210-222
    CrossrefPubMedGoogle Scholar
  • 42 Crisby M, Rahman SMA, Sylvén C et al. Effects of high cholesterol diet on gliosis in apolipoprotein E knockout mice: Implications for Alzheimer’s disease and stroke. Neuroscience Letters 2004; 369: 87-92
    CrossrefPubMedGoogle Scholar
  • 43 Montilla P, Espejo I, Muñoz MC et al. Protective effect of red wine on oxidative stress and antioxidant enzyme activities in the brain and kidney induced by feeding high cholesterol in rats. Clinical Nutrition 2006; 25: 146-153
    CrossrefPubMedGoogle Scholar
  • 44 Gosselet F, Saint-Pol J, Fenart L. Effects of oxysterols on the blood–brain barrier: Implications for Alzheimer’s disease. Biochemical and Biophysical Research Communications 2013; In press
    PubMedGoogle Scholar
  • 45 Poli G, Biasi F, Leonarduzzi G. Oxysterols in the pathogenesis of major chronic diseases. Redox Biology 2013; 1: 125-130
    CrossrefPubMedGoogle Scholar
  • 46 Emanuelsson I, Norlin M. Protective effects of 27- and 24-hydroxycholesterol against staurosporine-induced cell death in undifferentiated neuroblastoma SH-SY5Y cells. Neuroscience Letters 2012; 525: 44-48
    CrossrefPubMedGoogle Scholar
  • 47 Kölsch H, Heun R, Kerksiek A et al. Altered levels of plasma 24S- and 27-hydroxycholesterol in demented patients. Neuroscience Letters 2004; 368: 303-308
    CrossrefPubMedGoogle Scholar
  • 48 Leoni V, Caccia C. 24S-hydroxycholesterol in plasma: A marker of cholesterol turnover in neurodegenerative diseases. Biochimie 2013; In Press: In Press
    PubMedGoogle Scholar
  • 49 Tan C-C, Yu J-T, Tan M-S et al. Autophagy in aging and neurodegenerative diseases: implications for pathogenesis and therapy. Neurobiology of Aging 2013; In press
    PubMedGoogle Scholar
  • 50 Floyd RA, Hensley K. Oxidative stress in brain aging: Implications for therapeutics of neurodegenerative diseases. Neurobiology of Aging 2002; 23: 795-807
    CrossrefPubMedGoogle Scholar
  • 51 Mariani E, Polidori MC, Cherubini A et al. Oxidative stress in brain aging, neurodegenerative and vascular diseases: An overview. Journal of Chromatography B 2005; 827: 65-75
    CrossrefPubMedGoogle Scholar
  • 52 Gamaley IA, Klyubin IV. Roles of Reactive Oxygen Species: Signaling and Regulation of Cellular Functions. Academic Press 1999
    PubMedGoogle Scholar
  • 53 Yuan Y, Bian JC, Liu XZ et al. Oxidative Stress and Apoptotic Changes of Rat Cerebral Cortical Neurons Exposed to Cadmium in Vitro. Biomedical and Environmental Sciences 2012; 25: 172-181
    PubMedGoogle Scholar
  • 54 Brasnjevic I, Hof PR, Steinbusch HWM et al. Accumulation of nuclear DNA damage or neuron loss: Molecular basis for a new approach to understanding selective neuronal vulnerability in neurodegenerative diseases. DNA Repair 2008; 7: 1087-1097
    CrossrefPubMedGoogle Scholar
  • 55 Saxena S, Caroni P. Selective Neuronal Vulnerability in Neurodegenerative Diseases: from Stressor Thresholds to Degeneration. Neuron 2011; 71: 35-48
    CrossrefPubMedGoogle Scholar
  • 56 Surmeier DJ. Calcium, ageing, and neuronal vulnerability in Parkinson’s disease. The Lancet Neurology 2007; 6: 933-938
    CrossrefPubMedGoogle Scholar
  • 57 Butterfield DA, Galvan V, Lange MB et al. In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid β-peptide of APP. Free Radical Biology and Medicine 2010; 48: 136-144
    CrossrefPubMedGoogle Scholar
  • 58 Butterfield DA, Reed T, Newman SF et al. Roles of amyloid β-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer’s disease and mild cognitive impairment. Free Radical Biology and Medicine 2007; 43: 658-677
    CrossrefPubMedGoogle Scholar
  • 59 Li G, Zou L, Jack Jr CR et al. Neuroprotective effect of Coenzyme Q10 on ischemic hemisphere in aged mice with mutations in the amyloid precursor protein. Neurobiology of Aging 2007; 28: 877-882
    CrossrefPubMedGoogle Scholar
  • 60 Moreira PI, Santos MS, Sena C et al. CoQ10 therapy attenuates amyloid β-peptide toxicity in brain mitochondria isolated from aged diabetic rats. Experimental Neurology 2005; 196: 112-119
    CrossrefPubMedGoogle Scholar
  • 61 Ishrat T, Khan MB, Hoda MN et al. Coenzyme Q10 modulates cognitive impairment against intracerebroventricular injection of streptozotocin in rats. Behavioural Brain Research 2006; 171: 9-16
    CrossrefPubMedGoogle Scholar