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Recovery of Age-Related Memory Loss: Hopes and Challenges

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Topics in Biomedical Gerontology

Abstract

Advancing age is associated with drastic decline in memory and is a predisposing factor for neurodegenerative and neuropsychiatric disorders. Such decline results from aging of the brain involving loss of morphological integrity, alterations at the level of genes, enzymes and hormones, metabolism, oxidative stress, protein processing and synaptic function. Multiple biological scales ranging from genes to neural network and behavior and the individual variability that span age associated memory loss have added complexity to the recovery strategies. However, recent advancement in neuroscience research has not only removed the myth of unrecoverable memory loss during aging but also proposed a multitude of recovery approaches. These approaches include herbal interventions, dietary restrictions, antioxidant supplementation, environmental enrichment, lifestyle modulation and molecular targeting. Our laboratory is particularly interested in unraveling the molecular mechanism of age related memory loss and delineate therapeutic targets. Studies on animal models and humans reveal drastic changes in the expression and function of a wide array of molecules including chromatin modifying enzymes, immediate early genes, neurotrophins, presynaptic and postsynaptic proteins and neurite growth markers in vulnerable brain regions of cerebral cortex and hippocampus during aging. Such molecular changes are well translated into behavioral paradigms of memory impairment. In this chapter, we review age associated changes in brain, mechanisms of memory loss and recovery strategies. Essentially, we highlight the molecular correlates of brain aging and their potential as therapeutic targets for age associated memory loss.

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References

  • Abel T, Lattal KM (2001) Molecular mechanisms of memory acquisition, consolidation and retrieval. Curr Opin Neurobiol 11:180–187

    Article  CAS  PubMed  Google Scholar 

  • Benice TS, Rizk A, Kohama S, Pfankuch T, Raber J (2006) Sex differences in age-related cognitive decline in C57BL/6 J mice associated with increased brain microtubule-associated protein 2 and synaptophysin immunoreactivity. Neuroscience 137:413–423

    Article  CAS  PubMed  Google Scholar 

  • Berti V, Mosconi L, Glodzik L, Li Y, Murray J et al (2011) Structural brain changes in normal individuals with a maternal history of Alzheimer’s. Neurobiol Aging 32:2325

    Article  PubMed  PubMed Central  Google Scholar 

  • Blalock EM, Chen K, Sharrow K, Herman JP, Porter NM, Foster TC, Landfield PW (2003) Gene microarrays in hippocampal aging: statistical profiling identifies novel processes correlated with cognitive impairment. J Neurosci 23:3807–3819

    CAS  PubMed  Google Scholar 

  • Bramham CR, Worley PF, Moore MJ, Guzowski JF (2008) The immediate early gene Arc/Arg3.1: regulation, mechanisms, and function. J Neurosci 28:11760–11767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Budni J, Bellettini-Santos T, Mina F, Garcez ML, Zugno AI (2015) The involvement of BDNF. NGF and GDNF in aging and Alzheimer’s disease. Aging Dis. doi:10.14336/AD.2015.0825

  • Burger C (2010) Region-specific genetic alterations in the aging hippocampus: implications for cognitive aging. Front Aging Neurosci 2:1–8

    Article  Google Scholar 

  • Burke SN, Barnes CA (2006) Neural plasticity in the ageing brain. Nat Rev Neurosci 7:30–40

    Article  CAS  PubMed  Google Scholar 

  • Chakrabarti S, Munshi S, Banerjee K, Thakurta IG, Sinha M, Bagh MB (2007) Mitochondrial dysfunction during brain aging: Role of oxidative stress and modulation by antioxidant supplementation. Aging Dis 2:242–256

    Google Scholar 

  • Chang L, Jiang CS, Ernst T (2009) Effects of age and sex on brain glutamate and other metabolites. Mag Res Ima 27:142–145

    Article  CAS  Google Scholar 

  • Colcombe S, Kramer AF (2003) Fitness effects on the cognitive function of older adults; a meta-analytic study. Psychol Sci 14:125–130

    Article  PubMed  Google Scholar 

  • Deary IJ, Corley J, Aj Gow, Harris SE, Houlihan LM et al (2009) Age-associated cognitive decline. Brit Med Bull 92:135–152

    Article  PubMed  Google Scholar 

  • den Dunnen WF, Brouwer WH, Bijlard E, Kamphuis J, van Linschoten K, Eggens-Meijer E, Holstege G (2008) No disease in the brain of a 115-year-old woman. Neurobiol Aging 29:1127–1132

    Article  Google Scholar 

  • Desjardins S, Mayo W, Vallee M, Hancock D, Le Moal M, Simon H, Abrous DN (1997) Effect of aging on the basal expression of c-Fos, c-Jun, and Egr-1 proteins in the hippocampus. Neurobiol Aging 18:37–44

    Google Scholar 

  • deToledo-Morrell L, Geinisman Y, Morrell F (1988) Age-dependent alterations in haippocampal synaptic plasticity: Relation to memory disorders. Neurobiol Aging 9:581–590

    Article  CAS  PubMed  Google Scholar 

  • Drachman DA, Noffsinger D, Sahakian BJ, Kurdziel S, Fleming P (1979) Aging, memory and cholinergic system: A study of dichotic listening. Ann Neurol 6:157–158

    Google Scholar 

  • Erickson KI, Prakash RS, Voss MW, Chaddock L, Heo S et al (2010) Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume. J Neurosci 30:5368–5375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng J, Zhou Y, Campbell SL, Le T, Li E et al (2010) Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nat Neurosci 13:423–430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foster TC (1999) Involvement of hippocampal synaptic plasticity in age related memory decline. Brain Res Rev 30:236–249

    Article  CAS  PubMed  Google Scholar 

  • Foster TC (2007) Calcium homeostasis and modulation of synaptic plasticity in the aged brain. Aging Cell 6:319–325

    Article  CAS  PubMed  Google Scholar 

  • Gautam A, Kaul S, Thakur MK (2015) Alcoholic extract of ashwagandha leaves protects against amnesia by regulation of Arc function. Neurobiol, Mol. doi:10.1007/s12035-015-9117-2

    Google Scholar 

  • Gautam A, Wadhwa R, Thakur MK (2013) Involvement of hippocampal Arc in amnesia and its recovery by alcoholic extract of Ashwagandha leaves. Neurobiol Learn Mem 106:177–184

    Article  PubMed  Google Scholar 

  • Glisky EL (2007) Changes in cognitive function in human aging; in Brain Aging: models, methods, and mechanisms. In: Riddle DR (ed). CRC Press

    Google Scholar 

  • Guan JS, Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N et al (2009) HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459:55–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hermann PM, Watson SN and Wildering WC (2014) Phospholipase A2- nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment. Front Genet. doi:10.3389/fgene.2014.00419

  • Intlekofer KA, Berchtold NC, Malvaez M, Carlos AJ, McQuown SC et al (2013) Exercise and sodium butyrate transform a subthreshold learning event into long-term memory via a brain-derived neurotrophic factor- dependent mechanism. Neuropsychopharmacology 38:2027–2034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacobs B, Schall M, Prather M, Kapler E, Driscoll L et al (2001) Regional dendritic and spine variations in human cerebral cortex: a quantitative Golgi study. Cereb Cortex 11:558–571

    Article  CAS  PubMed  Google Scholar 

  • Knapskaa E and Kaczmarek L (2004) A gene for neuronal plasticity in the mammalian brain: Zif268/Egr-1/NGFI-A/Krox-24/TIS8/ZENK? Prog Neurobiol 74:183–211

    Google Scholar 

  • Konar A, Thakur MK (2015) Neuropsin expression correlates with dendritic marker MAP2c level in different brain regions of aging mice. Mol Neurobiol 51:1130–1138

    Article  CAS  PubMed  Google Scholar 

  • Konar A, Gautam A, Thakur MK (2015a) Bacopa monniera (CDRI-08) upregulates the expression of neuronal and glial plasticity markers in the brain of scopolamine-induced amnesic mice. Evi Based Compl Alt Med id:837012

    Google Scholar 

  • Konar A, Shah N, Singh R, Saxena N, Kaul SC, Wadhwa R, Thakur MK (2011) Protective role of Ashwagandha leaf extract and its component withanone on scopolamine induced changes in the brain and brain-derived cells. PLoS ONE. doi:10.1371/journal.pone.0027265

    Google Scholar 

  • Konar A, Singh P, Thakur MK (2015b) Age-associated cognitive decline: Insights into molecular switches and recovery avenues. Aging Dis. doi:10.14336/AD.2015.1004

    Google Scholar 

  • Kramer AF, Bherer L, Colcombe SJ, Dong W, Greenough WT (2004) Environmental influences on cognitive and brain plasticity during aging. J Gerontol A Biol Sci Med Sci 59:940–957

    Article  Google Scholar 

  • Kubik S, Miyashita T, Guzowski JF (2007) Using immediate-early genes to map hippocampal subregional functions. Learn Mem 14:758–770

    Article  PubMed  Google Scholar 

  • Kumar D, Thakur MK (2015) Age-related expression of Neurexin1 and Neuroligin3 is correlated with presynaptic density in the cerebral cortex and hippocampus of male mice. Age. doi:10.1007/s11357-015-9752-6

    PubMed  PubMed Central  Google Scholar 

  • Kumari A, Thakur MK (2014) Age-dependent decline of nogo-a protein in the mouse cerebrum. Cell Mol Neurobiol 34:1131–1141

    Article  CAS  PubMed  Google Scholar 

  • Lemura LM, von Duvillard SP, Mookerjee S (2000) The effects of physical training of functional capacity in adults. Ages 46 to 90: a meta-analysis. J Sports Med Phys Fitness 40:1–10

    CAS  PubMed  Google Scholar 

  • Lu T, Pan Y, Kao S, Li C, Kohane I, Chan J, Yankner BA (2004) Gene regulation and DNA damage in the aging human brain. Nature 429:883–891

    Article  CAS  PubMed  Google Scholar 

  • Lupien SJ, McEwen BS, Gunnar MR, Heim C (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10:434–445

    Article  CAS  PubMed  Google Scholar 

  • Martin M, Zimprich D (2003) Are changes in cognitive functioning in older adults related to changes in subjective complaints? Exp Aging Res 29:335–352

    Article  PubMed  Google Scholar 

  • McDougall GJ (2000) Memory improvement in assisted living elders. Issues Ment Health Nurs 21:217–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mora F, Segovia G, del Arco A (2007) Aging, plasticity and environmental enrichment: Structural changes and neurotransmitter dynamics in several areas of the brain. Brain Res Rev 55:78–88

    Article  CAS  PubMed  Google Scholar 

  • Morris MC (2006) Nutrition and cognitive aging. Modifiers of cognitive aging; friedman conference St. Louis: Washington University Center for Aging 1–30

    Google Scholar 

  • Nagata Y, Uehara T, Kitamura Y, Nomura Y, Horiike K (1998) D-serine and D-[3H]serine binding in the brain regions of senescence-accelerated mouse. Mech Aging Dev 104:115–124

    Article  CAS  PubMed  Google Scholar 

  • Newson RS, Kemps EB (2006) The nature of subjective cognitive complaints of older adults. Int J Aging Hum Dev 63:139–151

    Article  PubMed  Google Scholar 

  • Okuno H (2011) Regulation and function of immediate-early genes in the brain: Beyond neuronal activity markers. Neurosci Res 69:175–186

    Article  CAS  PubMed  Google Scholar 

  • Ota M, Yasuno F, Ito H, Seki C, Nozaki S, Asada T, Suhara T (2006) Age-related decline of dopamine synthesis in the living human brain measured by positron emission tomography with L-[beta-11C]DOPA. Life Sci 79:730–736

    Article  CAS  PubMed  Google Scholar 

  • Paramanik V, Thakur MK (2013) Role of CREB signaling in aging brain. Arch Ital Biol 151:33–42

    CAS  PubMed  Google Scholar 

  • Peinado MA, Quesada A, Pedrosa JA, Martinez M, Esteban FJ, Del Moral ML, Peinado JM (1997) Light Microscopic quantification of morphological changes during aging in neurons and glia of the rat parietal cortex. Anat Rec 247:420–425

    Article  CAS  PubMed  Google Scholar 

  • Peleg S, Sananbenesi F, Zovoilis A, Burkhardt S, Bahari-Javan S et al (2010) Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 753:328–333

    Google Scholar 

  • Penner MR, Roth TL, Chawla MK, Hoanga LT, Roth ED et al (2011) Age-related changes in Arc transcription and DNA methylation within the hippocampus. Neurobiol Aging 32:2198–2210

    Article  CAS  PubMed  Google Scholar 

  • Perry EK, Blessed G, Tomlinson BE, Perry RH, Crow TJ et al (1981) Neurochemical activities in human temporal lobe related to aging and Alzheimer-type changes. Neurobiol Aging 2:251–256

    Article  CAS  PubMed  Google Scholar 

  • Pinton P, Ferrari D, Rapizzi E, Di Virgilio F, Pozzan T, Rizzuto R (2001) The Ca2+ concentration of the endoplasmic reticulum is a key determinant of ceramide-induced apoptosis: significance for the molecular mechanism of Bcl-2 action. EMBO J 20:2690–2701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Radak Z, Marton O, Nagy E, Koltai E, Goto S (2013) The complex role of physical exercise and reactive oxygen species on brain. J Sport Health Sci 2:87–93

    Article  Google Scholar 

  • Reolon GK, Maurmann N, Werenicz A, Garcia VA, Schröder N, Wood MA et al (2011) Posttraining systemic administration of the histone deacetylase inhibitor sodium butyrate ameliorates aging-related memory decline in rats. Behav Brain Res 221:329–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rowe WB, Blalock EM, Chen KC, Kadish I, Wang D, Barrett JF, Thibault O, Porter NM, Rose GM, Landfield PW (2007) Hippocampal expression analyses reveal selective association of immediate-early, neuroenergetic, and myelinogenic pathways with cognitive impairment in aged rats. J Neurosci 27:3098–3110

    Article  CAS  PubMed  Google Scholar 

  • Salthouse TA (2003) Memory aging from 18 to 80. Alzheimer Dis Assoc Disord 17:162–167

    Article  PubMed  Google Scholar 

  • Sandyk R (1997) The accelerated aging hypothesis of Parkinson’s disease is not supported by the pattern of circadian melatonin secretion. Int J Neurosci 90:271–275

    Article  CAS  PubMed  Google Scholar 

  • Schmidt R, Schmidt H, Haybaeck J, Loitfelder M, Weis S, Cavalieri M, Seiler S, Enzinger C, Ropele S et al (2011) Heterogeneity in age-related white matter changes. Acta Neuropathol 122:171–185

    Article  PubMed  Google Scholar 

  • Schumacher M, Weill-Engerer S, Liere P, Robert F, Franklin RJM, Garcia-Segura LM, Lambert JJ, Mayoe W, Melcangi RC et al (2003) Steroid hormones and neurosteroids in normal and pathological aging of the nervous system. Prog Neurobiol 71:3–29

    Article  CAS  PubMed  Google Scholar 

  • Singh P, Thakur MK (2014) Reduced recognition memory is correlated with decrease in DNA methyltransferase1 and increase in histone deacetylase2 protein expression in old male mice. Biogerontology 15:339–346

    Article  CAS  PubMed  Google Scholar 

  • Singh P, Konar A, Kumar A, Srivas S, Thakur MK (2015) Hippocampal chromatin-modifying enzymes are pivotal for scopolamine-induced synaptic plasticity gene expression changes and memory impairment. J Neurochem. doi:10.1111/jnc.13171

    PubMed Central  Google Scholar 

  • Smith RG, Betancourt L, Sun Y (2005) Molecular endocrinology and physiology of the aging central nervous system. Endocr Rev 26:203–250

    Article  CAS  PubMed  Google Scholar 

  • Sorra KE, Harris KM (2000) Overview on the structure, composition, function, development, and plasticity of hippocampal dendritic spines. Hippocampus 10:501–551

    Article  CAS  PubMed  Google Scholar 

  • Tapia-Arancibia L, Aliaga E, Silhol M, Arancibia S (2008) New insights into brain BDNF function in normal aging and Alzheimer disease. Brain Res Rev 59:201–220

    Article  CAS  PubMed  Google Scholar 

  • Thakur MK, Rattan SIS (2012) Brain aging and therapeutic interventions. Springer Publication

    Google Scholar 

  • Thakur MK, Konar A (2014) Brain Aging and associated diseases; in Text book on geriatric medicine. In: Sanchetee P (ed). Paras Medical Publisher, pp 32–36

    Google Scholar 

  • Thakur MK, Konar A, Gautam A (2012) Brain aging: A critical reappraisal; in Brain Aging and Therapeutic Interventions. In: Thakur MK, Rattan SIS (eds). Springer Science, pp 1–18

    Google Scholar 

  • Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol 15:335–344

    Article  Google Scholar 

  • Tzingounis A, Nicoll RA (2006) Arc/Arg3.1: Linking gene expression to synaptic plasticity and memory. Neuron 52:403–407

    Article  CAS  PubMed  Google Scholar 

  • van Luijtelaar MG, Tonnaer JA, Steinbusch HW (1992) Aging of the serotonergic system in the rat forebrain: An immunocytochemical and neurochemical study. Neurobiol Aging 13:201–215

    Article  PubMed  Google Scholar 

  • Veiga S, Melcangib RC, Doncarlosc LL, Garcia-Seguraa LM, Azcoitiad I (2004) Sex hormones and brain aging. Exp Gerontol 39:1623–1631

    Article  CAS  PubMed  Google Scholar 

  • Verhaeghen P, Salthouse TA (1997) Meta-analyses of age-cognition relations in adulthood: estimates of linear and nonlinear age effects and structural models. Psycho Bull 122:231–249

    Article  CAS  Google Scholar 

  • Wenk GL, Barnes CA (2000) Regional changes in the hippocampal density of AMPA and NMDA receptors across the lifespan of the rat. Brain Res 885:1–5

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto M (2001) Depression in Parkinson’s disease: its prevalence, diagnosis, and neurochemical background. J Neurol 248:5–11

    Article  Google Scholar 

  • Yankner BA, Lu T, Loerch P (2008) The aging brain. Annu Rev Pathol Mech Dis 3:41–66

    Article  CAS  Google Scholar 

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Acknowledgments

The authors thank Department of Science and Technology (DST), Government of India for INSPIRE faculty award to AK. PS and DK are recipient of Senior Research Fellowship from the Council of Scientific and Industrial Research (CSIR) Government of India, and MSB is a recipient of Junior Research Fellowship from Department of Biotechnology (DBT) Government of India. The work cited in this article has been supported by grants from the DBT, DST, CSIR, ICMR, Government of India, to MKT.

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Thakur, M.K., Konar, A., Kumar, D., Baghel, M.S., Singh, P. (2017). Recovery of Age-Related Memory Loss: Hopes and Challenges. In: Rath, P., Sharma, R., Prasad, S. (eds) Topics in Biomedical Gerontology. Springer, Singapore. https://doi.org/10.1007/978-981-10-2155-8_14

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