Generic placeholder image

Current Aging Science

Editor-in-Chief

ISSN (Print): 1874-6098
ISSN (Online): 1874-6128

Research Article

Behavioral Assessment and Blood Oxidative Status of Aging Sprague Dawley Rats through a Longitudinal Analysis

Author(s): Nurul A. Achin, Tan J. Kit, Wan Z.W. Ngah, Suzana Makpol, Musalmah Mazlan, Hamizah S. Hamezah and Hanafi A. Damanhuri*

Volume 11, Issue 3, 2018

Page: [182 - 194] Pages: 13

DOI: 10.2174/1874609811666181019141217

Price: $65

Abstract

Background: Cognitive frailty emerges as one of the threats to healthy aging. It is in continuum with advancing of age with uncertain indicator between pathological and physiological changes. Alterations in pathways associated with the aging process have been observed including oxidative stress, lipid metabolism, and inflammation. However, the exact mechanisms leading to cognitive decline are still unclear.

Objective: This study was sought to assess the level of cognitive functions and linked with blood oxidative status during normal aging in rats.

Methods: A longitudinal study using male Sprague Dawley rats was performed starting from the age of 14 months old to 27 months old. Cognitive functions tests such as open field, Morris water maze and object recognition were determined at the age of 14, 18, 23, and 27 months old and were compared with group 3 months old. Blood was collected from the orbital venous sinus and oxidative status was determined by measuring the level of DNA damage, lipid peroxidation, protein oxidation and antioxidant enzymes activity.

Results: Aged rats showed declining exploratory behavior and increased in the level of anxiety as compared to the young rats. The level of DNA damage increased with increasing age. Interestingly, our study found that both levels of malondialdehyde and plasma carbonyl content decreased with age. In addition, the level of superoxide dismutase activity was significantly decreased with age whereas catalase activity was significantly increased from 18 months of age. However, no significant difference was found in glutathione peroxidase activity among all age groups.

Conclusion: The progressions of cognitive impairment in normal aging rats are linked to the increment in the level of DNA damage.

Keywords: Cognitive decline, normal aging, rat, longitudinal, oxidative status, DNA damage.

Graphical Abstract
[1]
Floyd RA, Hensley K. Oxidative stress in brain aging: Implications for therapeutics of neurodegenerative diseases. Neurobiol Aging 2002; 23(5): 795-807.
[2]
Glisky EL. Changes in cognitive function in human aging. Brain Aging Models Meth Mech 2007; pp. 3-20.
[3]
Gage FH, Dunnett SB, Björklund A. Spatial learning and motor deficits in aged rats. Neurobiol Aging 1984; 5(1): 43-8.
[4]
Geinisman Y, Ganeshina O, Yoshida R, et al. Aging, spatial learning, and total synapse number in the rat CA1 stratum radiatum. Neurobiol Aging 2004; 25(3): 407-16.
[5]
Moffat SD, Resnick SM. Effects of age on virtual environment place navigation and allocentric cognitive mapping. Behav Neurosci 2002; 116(5): 851.
[6]
Frick KM, Baxter MG, Markowska AL, et al. Age-related spatial reference and working memory deficits assessed in the water maze. Neurobiol Aging 1995; 16(2): 149-60.
[7]
Zelazo PD, Craik FI, Booth L. Executive function across the life span. Acta Psychol 2004; 115(2): 167-83.
[8]
Forster MJ, Dubey A, Dawson KM, et al. Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain. Proc Natl Acad Sci 1996; 93(10): 4765-9.
[9]
Liua P, Smitha PF, Appletona I, et al. Potential involvement of NOS and arginase in age-related behavioural impairments. Exp Gerontol 2004; 39(8): 1207.
[10]
Reddy PH, Beal MF. Amyloid beta, mitochondrial dysfunction and synaptic damage: Implications for cognitive decline in aging and Alzheimer’s disease. Trends Mol Med 2008; 14(2): 45-53.
[11]
Kristine YMD, Alka KMD, Karla LMS, et al. The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA 2004; 292(18): 2237-42.
[12]
Claudine B, Bertrand BMD, Josianne A, et al. Cognitive decline is associated with systemic oxidative stress: The EVA study. J Am Geriatr Soc 2000; 48(10): 1285-91.
[13]
Dröge W, Schipper HM. Oxidative stress and aberrant signaling in aging and cognitive decline. Aging Cell 2007; 6(3): 361-70.
[14]
Koji F, Nao‐omi O, Takahiro H, et al. Cognitive impairment of rats caused by oxidative stress and aging, and its prevention by vitamin E. Annals New York Acad Sci 2002; 959(1): 275-84.
[15]
Sies H. Oxidative stress: Introductory remarks. Oxidative stress, 1985: p. 1-8
[16]
MatÉs JM. Pérez-Gómez C, De Castro IN. Antioxidant enzymes and human diseases. Clin Biochem 1999; 32(8): 595-603.
[17]
Sies H. Oxidative stress: Oxidants and antioxidants. Exp Physiol 1997; 82(2): 291-5.
[18]
Kregel KC, Zhang HJ. An integrated view of oxidative stress in aging: Basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol 2007; 292(1): R18-36.
[19]
Golden TR, Hinerfeld DA, Melov S. Oxidative stress and aging: Beyond correlation. Aging Cell 2002; 1(2): 117-23.
[20]
Michelle LH, Van Remmen H, Jessica AD, et al. Does oxidative damage to DNA increase with age? Proc Natl Acad Sci 2001; 98(18): 10469-74.
[21]
Sohal RS, Agarwal S, Dubey A, et al. Protein oxidative damage is associated with life expectancy of houseflies. Proc Natl Acad Sci 1993; 90(15): 7255-9.
[22]
Stadtman ER. Protein oxidation in aging and age‐related diseases. Ann N Y Acad Sci 2001; 928(1): 22-38.
[23]
Yan LJ, Sohal RS. Mitochondrial adenine nucleotide translocase is modified oxidatively during aging. Proc Natl Acad Sci USA 1998; 95(22): 12896-901.
[24]
Naoaki I, Michihiko F, Philip S, et al. A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature 1998; 394(6694): 694-7.
[25]
Simon M, Pinar C, Manisha P, et al. Mitochondrial disease in superoxide dismutase 2 mutant mice. Proc Natl Acad Sci 1999; 96(3): 846-51.
[26]
Heather MS, Maria CC, Francine G, et al. Developing novel blood-based biomarkers for Alzheimer’s disease. Alzheimers Dement 2014; 10(1): 109-14.
[27]
Nursiati MT, Nazirah AR, Azian AL, et al. Tocotrienol rich fraction reverses age-related deficits in spatial learning and memory in aged rats. Lipids 2014; 49(9): 855.
[28]
Hamizah SH, Lina WD, Faeizah I, et al. Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions. Exp Gerontol 2017; 99: 69-79.
[29]
Sahhugi Z, Hasenan SM, Jubri Z. Protective effects of gelam honey against oxidative damage in young and aged rats. Oxid Med Cell Longev 2014; 2014
[http://dx.doi.org/10.1155/2014/673628]
[30]
Narendra PS, Michael TM, Raymond RT, et al. A simple technique for quantitation of low levels of DNA damage in individual cells. Experiment Cell Res 1988; 175(1): 184-91.
[31]
Michelle MA, Lei SM, Constance L, et al. Caloric restriction and age affect synaptic proteins in hippocampal CA3 and spatial learning ability. Exp Neurol 2008; 211(1): 141-9.
[32]
Hebda-Bauer EK, Morano MI, Therrien B. Aging and corticosterone injections affect spatial learning in Fischer-344× Brown Norway rats. Brain Res 1999; 827(1): 93-103.
[33]
Markowska AL, Savonenko A. Retardation of cognitive aging by life-long diet restriction: Implications for genetic variance. Neurobiol Aging 2002; 23(1): 75-86.
[34]
Rönnlund M, Nyberg L, Backman L, et al. Stability, growth, and decline in adult life span development of declarative memory: Cross-sectional and longitudinal data from a population-based study. Psychol Aging 2005; 20(1): 3-18.
[35]
Marja JA, Carolien HMS. Theo van T, et al. Activity in older adults cause or consequence of cognitive functioning? A longitudinal study on everyday activities and cognitive performance in older adults. J Gerontol B Psychol Sci Soc Sci 2002; 57(2): 153-62.
[36]
Dellu F, Mayo W, Vallee M, et al. Facilitation of cognitive performance in aged rats by past experience depends on the type of information processing involved: A combined cross-sectional and longitudinal study. Neurobiol Learn Mem 1997; 67(2): 121-8.
[37]
Barnes CA. Memory deficits associated with senescence: A neurophysiological and behavioral study in the rat. J Comp Physiol Psychol 1979; 93(1): 74.
[38]
Craik FI, Byrd M, Swanson JM. Patterns of memory loss in three elderly samples. Psychol Aging 1987; 2(1): 79.
[39]
Wallace JE, Krauter EE, Campbell BA. Animal models of declining memory in the aged: Short-term and spatial memory in the aged rat. J Gerontol 1980; 35(3): 355-63.
[40]
Algeri S, Biagini L, Manfridi A, et al. Age-related ability of rats kept on a life-long hypocaloric diet in a spatial memory test. Longitudinal observations. Neurobiol Aging 1991; 12(4): 277-82.
[41]
Carola V, D’Olimpio F, Brunamonti E, et al. Evaluation of the elevated plus-maze and open-field tests for the assessment of anxiety-related behaviour in inbred mice. Behav Brain Res 2002; 134(1): 49-57.
[42]
Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: A review. Eur J Pharmacol 2003; 463(1): 3-33.
[43]
Baeza I, De Castro NM, Giménez-Llort L, et al. Ovariectomy, a model of menopause in rodents, causes a premature aging of the nervous and immune systems. J Neuroimmunol 2010; 219(1): 90-9.
[44]
Luparini MR, Del Vecchio A, Barillari G, et al. Cognitive impairment in old rats: A comparison of object displacement, object recognition and water maze. Aging Clin Exp Res 2000; 12(4): 264-73.
[45]
Platano D, Fattoretti P, Balietti M, et al. Long-term visual object recognition memory in aged rats. Rejuvenation Res 2008; 11(2): 333-9.
[46]
Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 1984; 11(1): 47-60.
[47]
Culley DJ, Baxter MG, Yukhananov R, et al. Long-term impairment of acquisition of a spatial memory task following isoflurane–nitrous oxide anesthesia in rats. J Am Soc Anesthesiol 2004; 100(2): 309-14.
[48]
Wyss JM, Chambless BD, Kadish I, et al. Age-related decline in water maze learning and memory in rats: Strain differences. Neurobiol Aging 2000; 21(5): 671-81.
[49]
Rapp PR, Gallagher M. Preserved neuron number in the hippocampus of aged rats with spatial learning deficits. Proc Natl Acad Sci 1996; 93(18): 9926-30.
[50]
Brouillette J, Quirion R. Transthyretin: A key gene involved in the maintenance of memory capacities during aging. Neurobiol Aging 2008; 29(11): 1721-32.
[51]
Ménard C, Quirion R. Successful cognitive aging in rats: A role for mGluR5 glutamate receptors, homer 1 proteins and downstream signaling pathways. PLoS One 2012; 7(1): e28666.
[52]
Vorhees CV, Williams MT. Assessing spatial learning and memory in rodents. ILAR J 2014; 55(2): 310-32.
[53]
Haider S. Age-related decrease in striatal DA produces cognitive deficits in male rats. J Pharm Nutr Sci 2011; 1(1)
[http://dx.doi.org/10.6000/1927-5951.2011.01.01.05]
[54]
Lukaszewska I, Radulska I. Object recognition is not impaired in old rats. J Experim Neurobiol 1994; 54: 143.
[55]
Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature 2000; 408(6809): 239-47.
[56]
Horvat P, Kubinova R, Pajak A, et al. Blood-based oxidative stress markers and cognitive performance in early old age: The Hapiee Study. Dement Geriatr Cogn Disord 2016; 42(5-6): 297-309.
[57]
Fraga CG, Shigenaga MK, Park JW, et al. Oxidative damage to DNA during aging: 8-hydroxy-2′-deoxyguanosine in rat organ DNA and urine. Proc Natl Acad Sci 1990; 87(12): 4533-7.
[58]
Kaneko T, Tahara S, Matsuo M. Non-linear accumulation of 8-hydroxy-2′-deoxyguanosine, a marker of oxidized DNA damage, during aging. Mutat Res Rev Mutat Res 1996; 316(5): 277-85.
[59]
Wang YJ, Ho YS, Lo MJ, et al. Oxidative modification of DNA bases in rat liver and lung during chemical carcinogenesis and aging. Chem Biol Interact 1995; 94(2): 135-45.
[60]
Anson RM, Sentürker S, Dizdaroglu M, et al. Measurement of oxidatively induced base lesions in liver from Wistar rats of different ages. Free Radic Biol Med 1999; 27(3): 456-62.
[61]
Myung HC, Hiroshi K, Susumu N, et al. Protection of DNA damage by dietary restriction. Free Radic Biol Med 1992; 12(6): 523-5.
[62]
Hirano T, Yamaguchi R, Asami S, et al. 8-Hydroxyguanine levels in nuclear DNA and its repair activity in rat organs associated with age. J Gerontol A Biol Sci Med Sci 1996; 51(5): B303-7.
[63]
Sai K, Takagi A, Umemura T, et al. Changes of 8-hydroxydeoxyguanosine levels in rat organ DNA during the aging process. J Environ Pathol Toxicol Oncol 1991; 11(3): 139-43.
[64]
Lovell MA, Markesbery WR. Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer’s disease. Nucleic Acids Res 2007; 35(22): 7497-504.
[65]
Yankner BA, Lu T, Loerch P. The aging brain. Annu. Rev Pathmechdis Mech Dis 2008; 3: 41-66.
[66]
İnal ME, Kanbak G, Sunal E. Antioxidant enzyme activities and malondialdehyde levels related to aging. Clin Chim Acta 2001; 305(1): 75-80.
[67]
Leutner S, Eckert A, Müller W. ROS generation, lipid peroxidation and antioxidant enzyme activities in the aging brain. J Neural Transm (Vienna) 2001; 108(8-9): 955-67.
[68]
Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 2000; 29(3): 222-30.
[69]
Harman D. Origin and evolution of the free radical theory of aging: A brief personal history, 1954–2009. Biogerontology 2009; 10(6): 773-81.
[70]
Chung HY, Song SH, Kim HJ, et al. Modulation of renal xanthine oxidoreductase in aging: Gene expression and reactive oxygen species generation. J Nutr Health Aging 1998; 3(1): 19-23.
[71]
Mendoza-Núñez VM, Mirna RR, Martha ASR, et al. Aging-related oxidative stress in healthy humans. Tohoku J Exp Med 2007; 213(3): 261-8.
[72]
Sasaki T, Unno K, Tahara S, et al. Age‐related increase of superoxide generation in the brains of mammals and birds. Aging Cell 2008; 7(4): 459-69.
[73]
Sawada M, Carlson JC. Changes in superoxide radical and lipid peroxide formation in the brain, heart and liver during the lifetime of the rat. Mech Ageing Dev 1987; 41(1): 125-37.
[74]
Speakman JR, Selman C. The free‐radical damage theory: Accumulating evidence against a simple link of oxidative stress to ageing and lifespan. BioEssays 2011; 33(4): 255-9.
[75]
Viviana IP, Holly Van R, Alex B, et al. The overexpression of major antioxidant enzymes does not extend the lifespan of mice. Aging Cell 2009; 8(1): 73-5.
[76]
Viviana IP, Alex BH. Van Remmen, et al. Is the oxidative stress theory of aging dead? Biochim Biophys Acta, Gen Subj 2009; 1790(10): 1005-14.
[77]
Youngmok CJ, Viviana IP, Wook S, et al. Overexpression of Mn superoxide dismutase does not increase life span in mice. J Gerontol A Biol Sci Med Sci 2009; 64(11): 1114-25.
[78]
Ryan D, Joshua JM, Filip M, et al. Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans. Genes Dev 2008; 22(23): 3236-41.
[79]
Gems D, Doonan R. Antioxidant defense and aging in C. elegans: Is the oxidative damage theory of aging wrong? Cell Cycle 2009; 8(11): 1681-7.
[80]
Yang W, Li J, Hekimi S. A measurable increase in oxidative damage due to reduction in superoxide detoxification fails to shorten the life span of long-lived mitochondrial mutants of Caenorhabditis elegans. Genetics 2007; 177(4): 2063-74.
[81]
Van Raamsdonk JM, Hekimi S. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet 2009; 5(2): e1000361.
[82]
Keller JN, Schmitt FA, Scheff SW, et al. Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 2005; 64(7): 1152-6.
[83]
Wang J, Xiong S, Xie C, et al. Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer’s disease. J Neurochem 2005; 93(4): 953-62.
[84]
Nils ZB, Monique CW, Ingrid P, et al. Accelerated age-related cognitive decline and neurodegeneration, caused by deficient DNA repair. J Neurosci 2011; 31(35): 12543-53.
[85]
Simpson JE, Paul GI, Fiona EM, et al. A neuronal DNA damage response is detected at the earliest stages of Alzheimer’s neuropathology and correlates with cognitive impairment in the Medical Research Council’s Cognitive Function and Ageing Study ageing brain cohort. Neuropathol Appl Neurobiol 2015; 41(4): 483-96.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy