Abstract
Aging is a process that presents various alterations in physiological, behavioral and neurochemical processes. It causes impairment of CNS functions which lead to changes in memory, cognition and other behavioral performances. Reports have shown that aging causes neurochemical alterations in various physiological functions. The aim of the present study was to evaluate the cognitive changes in relation to process of aging. For this 20 male rats were taken, 10 young (4-6 months) and 10 old (18-22 months). Morris Water Maze (MWM) test was performed to monitor changes in learning and memory while Object-Recognition Task (ORT) was performed to evaluate changes in cognitive function. After behavioral assessment decapitation was done and rat brain was dissected to isolate striatum. Then neurochemical analysis was performed by HPLC-EC to monitor changes in striatal DA and DOPAC levels. Results of behavioral tests showed that aged rats exhibited a significant impairment of long-term memory. While cognitive ability assessed by ORT was also impaired in aged rats. Neurochemical results showed that there was a significant decline in striatal dopamine (DA) concentration while its metabolite DOPAC was significantly increased in aged rats. Hence aging has a significant negative influence on cognitive functions. Age-related behavioral deficits may occur as a result of decline in DA levels in striatum leading to changes in memory and cognitive performance.
References
Hedden T, Gabrieli JD. 2004. Insights into the ageing mind: a view from cognitive neuroscience. Nat Rev Neurosci 5:87– 96.
Peters R. 2006. Ageing and the brain, Postgard Med J. February; 82 (964): 84-88.
Joseph J, Zhang L, Ravipati A, and Roth GS. 1995. Agingrelated changes in rat striatal DA receptor mRNA-containig neurons: A quantitative nonradioactive in situ hybridization study. The Journal of Neuroscience, March 1995, 15(3): 1735-1740.
Mara Mather and Laura L.Carstensen. 2005. Aging and motivated cognition: the positively effect in attention and memory; Trends in Cognitive Sciences Vol. 9 No. 10. 496- 502.
Balu M, Sangeetha P, Murali G, Panneeselvam Ch. 2005. Age-related oxidative protein damages in central nervous system of rats: modulatory role of Grape seed extract. Int.J Devl Neuroscience; 23: 501-7.
Alireza Sarkaki, Yaghoub Farbood, Mohammad Badavi. 2007. The effect of grape seed extract on spatial memory in aged male rats; Pak. J Med Sci. Vol. 23 No. 4. 561-565.
Salthouse TA.1996. The processing-speed theory of adult age differences in cognition. Psychol Rev; 103:403–428.
Kausler DH (1994): Learning and memory in normal aging. San Diego, Academic Press.
Bäckman Lars, Nathalie Ginovart, Roger A. Dixon, Tarja- Brita Robins Wahlin, Åke Wahlin, Christer Halldin, and Lars Farde. 2000. Age-related cognitive deficits mediated by changes in the striatal dopamine system; Am J Psychiatry; 157:635–637.
Kluger A, Gianutsos JG, Golomb J, Ferris S H, George AE, Frannssen E, Reisberg B. 1997. Patterns of motor impairment in normal aging, mild cognitive decline, and early Alzheimer’s disease. J Gerontol 52:28 –39.
Cox Karin M, Howard J. Aizenstein and Julie A. Fiez. 2008. Striatal outcome processing in healthy aging. Cognitive, Affective, & Behavioral Neuroscience, 8 (3), 304-317. Doi: 10.3758/CABN.8.3.304
Raz N, Karen M. Rodrigue, Kristen M. Kennedy, Denise Head, Faith Gunning-Dixon, and James D. Acker. 2003. Differential aging of the human striatum: Longitudinal evidence. AJNR Am J Neuroradiol 24: 1849-1856.
Crosson BA. 1992. Subcortical functions in language and memory. New York, Guilford. 80-110.
Lai H, Bowden DM, Horita A. 1987. Age-related decreases in dopamine receptors in the caudate nucleus and putamen of the rhesus monkey (Muc & A mulattu). Neurobiol aging 8: 4549.
Raz N., Torres IJ, & Acker JD. 1995. Age, gender, and hemispheric differences in human striatum: A quantitative review and new data from in vivo MRI morphometry. Neurobiology of Learning & Memory, 63, 133-142.
Volkow ND, Gur RC, Wang GJ, Fowler JS, Moberg PJ, Ding YS, Hitzemann R, Smith G, Logan J. 1998. Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. Am J Psychiatry; 155:344–349.
Wang Y, Chan GL, Holden JE, Dobko T, Mak E, Schulzer M, Huser JM, Snow BJ, Ruth TJ, Calne DB, Stoessl AJ. 1998. Age-dependent decline of dopamine D1 receptors in human brain: a PET study. Synapse; 30:56–61.
Nyberg L, Backman L. 2004. Cognitive aging: a view from brain imaging. In: Dixon R, Backman L, Nilsson L. Ed. New frontiers in cognitive ageing. Oxford: university Press. 135- 160.
Mukherjee J, Christian B, Dunigan K. et al. 2002. Brain imaging of 18F- Fally pride in normal volunteers: Blood analysis, distribution, test-retest studies and premilinary assessment of sensitivity to aging effects on dopamine D- 2/D-3 receptors. Synapse. 46170-188.
Van Dyck CH, Seibyl JP, Malison RT, Laruelle M, Wallace E, Zoghbi SS, Zea-Ponce Y, Baldwin RM, Charney DS, Hoffer; PB. 1995. Age-related decline in striatal dopamine transporter binding with iodine-123-beta-CITSPECT. J Nucl Med; 36: 1175–1181.
Mattson M, Maudsleey S, Martin B. 2004. BDNF and 5-HT; A dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci. 27589-594.
Haider S, Saleem S, Shamim S, Ahmed SP, Parveen T and Haleem DJ. 2004. Is Anorexia in thioacetamide-induced cirrohsis related to an altered brain serotonin concentration? Pol. J. Pharmacol., 56: 73-78.
Morris RG. 1981. Spatial localization does not depend on the presence of local cues. Learning and Motivation. 12, 239- 260.
Shukitt HB. 1999. The effects of aging and oxidative stress on psychomotor and cognitive behavior. Age, Vol.22, 9-17.
Srikumar BN, Bindu B, Priya V, Shankarnarayana Rao BS, Raju TR and Bindu M Kutty. 2004. Methods of assessment of learning and memory in rodents. Brain and Behavior. 145- 151.
Haider S, Khaliq S, Haleem DJ. 2007. Enhanced serotonergic neurotransmission in the hippocampus following tryptophan administration improves learning acquisition and memory consolidation in rats. Pharmacological Reports, 59, 53-57.
Ennaceur, A.; Delacour, J. 1988. A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data. Behavioral Brain Research. 31: 47-59.
Okuda S, Roozendaal B, and McGaugh LJ. 2004. Glucocorticoid effects on object recognition memory require training-associated emotional arousal. PNAS, Jan 20; Vol. 101, No. 3, 853-858.
Peremans K, Audenaert K, Blanckaert P, Jacobs F, Coopman F, Verschooten F, Van Bree H, Van Heeringen C, Mertens J, Slegers G, Dierckx R. 2002. Effects of aging on brain perfusion and serotonin-2A receptor binding in the normal canine brain measured with single photon emission tomography. Prog Neuropsychopharmacol Biol. Psychiatry. Dec; 26(7-8):1393-404.
Barnes C.A. 1990. Animal models of age-related cognitive decline. In F.Boller & J.Grafman Eds; Handbook of Neuropsychology, vol.4, pp. 169-195. Amsterdam: Elsevier Science Publishers B.V.
Kubanis, P., & Zornetzer, S.F. 1981. Age-related behavioral & neurobiological changes: A review with an emphasis on memory. Behavioral & Neural Biology, 31, 115-172.
Moscovitch, M., Winocur, G. 1992. The neuropsychology of memory & ageing. In F.I.M. Craik & T.A.Salthouse Eds. The handbook of ageing & cognition, pp. 315-372. Mahwah, NJ: Erlbaum.
Gallagher M, Rapp PR. 1997. The use of animal models to study the effects of ageing on cognition. Annu Rev Psychol 48:339 –370.
Wilson IA, Gallagher M, Eichenbaum H, Tanila H. 2006. Neurocognitive ageing: prior memories hinder new hippocampal encoding. Trends Neurosci 29: 662– 670.
Albert MS. 1997. The ageing brain: normal and abnormal memory. Philos Trans R Soc Lond B Biol Sci 352:1703– 1709.
Buckner RL. 2004. Memory and executive function in ageing and AD: multiple factors that cause decline and reserve factors that compensate. Neuron 44:195–208.
Michael J. Forster, Anju Dubeyt, Kimberly M. Dawsont, William A stults, Harbans Lal and Rajindhar S. Sohalt T. 1996. Age- related losses of cognitive function and motor skills in mice are associarted with oxidative protein damage in the brain. Proc. Natl. Acad. Sci. USA Vol. 93, pp. 4765- 4769, Neurobiology.
Coyle, J. T. and Puttfarken, P. 1993. Oxidative stress, glutamate, and neurodegenerative disorders. Science 262, 689-695.
Halliwell, B. 1992. Reactive oxygen species and the central nervous system. J. Neurochem: 59, 1609-1623.
Sohal, R.S., Arnold L. A. and Sohal, B.H. 1990. Free Radical Biol. Med. 10, 495-500.
Lauren M. Willis, Barbara Shukitt-Hale, Vivian Cheng and James A. Joseph. 2009. Dose-dependent effects of walnuts on motor and cognitive function in aged rats; British Journal of Nutrition, 101, 1140-1144.
Maria Noêmia M. de Lima, Daniela C. Laranja, Fábio Caldana, Elke Bromberg, Rafael Roesler and Nadja Schröder. 2005. Reversal of age-related deficits in object recognition memory in rats with l-deprenyl. Experimental Gerontology; Volume 40, Issue 6, June 2005, Pages 506- 511.
Irwin I, Finnegan KT, Delanney LE, Di Monte D, Langston JW. 1992. The relationships between aging, monoamine oxidase, striatal dopamine and the effects of MPTP in C57BL/6 mice: a critical reassessment. Brain Res. Feb 14; 572 (1-2): 224-31.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.