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Published in: Journal of Neural Transmission 1/2015

01-08-2015 | Psychiatry and Preclinical Psychiatric Studies - Review article

Mechanisms underlying the neuroprotective effect of brain reserve against late life depression

Authors: Thomas Freret, Pierrette Gaudreau, Pascale Schumann-Bard, Jean-Marie Billard, Aurel Popa-Wagner

Published in: Journal of Neural Transmission | Special Issue 1/2015

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Abstract

Depression is common and medically relevant illness that has been associated to a state of “accelerated aging” and can significantly compromise successful aging. In recent years, the concept of “brain reserve” has emerged to describe some individuals having an increased “baseline adaptive neuroplasticity”, providing greater dynamic capacity for adjusting and remodeling cortical circuits to various stressors. We hypothesize that brain reserve may have neuroprotective effects against late life depression. Here, we discuss the modulatory capacity of stress and corticosteroid hormones on hippocampal plasticity and neuronal viability in late life depression as well as the anti-depressive of ketamine and scopolamine mediated by stimulation of the mammalian target of rapamycin, increased inhibitory phosphorylation of GSK-3β, and increased synaptogenesis. This review shall shed light on complex neurobiological mechanisms that underpin late life depression and help to better understand neural correlates of resilience. Investigating how rat models of increased cognitive reserve mitigate a chronic mild stress-elicited depression will afford new insights in the search for new therapeutic targets to treat this neuropsychiatric disorder.
Literature
go back to reference Alliot J, Boghossian S, Jourdan D, Veyrat-Durebex C, Pickering G, Meynial-Denis D, Gaumet N (2002) The LOU/c/Jall rat as an animal model of healthy aging? J Gerontol 57(8):312–320CrossRef Alliot J, Boghossian S, Jourdan D, Veyrat-Durebex C, Pickering G, Meynial-Denis D, Gaumet N (2002) The LOU/c/Jall rat as an animal model of healthy aging? J Gerontol 57(8):312–320CrossRef
go back to reference Barzilai N, Bartke A (2009) Biological approaches to mechanistically understand the healthy life span extension achieved by calorie restriction and modulation of hormones. J Gerontol 64(2):187–191. doi:10.1093/gerona/gln061 CrossRef Barzilai N, Bartke A (2009) Biological approaches to mechanistically understand the healthy life span extension achieved by calorie restriction and modulation of hormones. J Gerontol 64(2):187–191. doi:10.​1093/​gerona/​gln061 CrossRef
go back to reference Berkman LF, Seeman TE, Albert M, Blazer D, Kahn R et al (1993) High, usual and impaired functioning in community-dwelling older men and women: findings from the MacArthur foundation research network on successful aging. J Clin Epidemiol 46(10):1129–1140PubMedCrossRef Berkman LF, Seeman TE, Albert M, Blazer D, Kahn R et al (1993) High, usual and impaired functioning in community-dwelling older men and women: findings from the MacArthur foundation research network on successful aging. J Clin Epidemiol 46(10):1129–1140PubMedCrossRef
go back to reference Berman R, Cappiello A, Anand A et al (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiat 47:351–354 (PubMed: 10686270)PubMedCrossRef Berman R, Cappiello A, Anand A et al (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiat 47:351–354 (PubMed: 10686270)PubMedCrossRef
go back to reference Calabrese F, Molteni R, Gabriel C, Mocaer E, Racagni G, Riva MA (2011) Modulation of neuroplastic molecules in selected brain regions after chronic administration of the novel antidepressant agomelatine. Psychopharmacology 215(2):267–275. doi:10.1007/s00213-010-2129-8 PubMedCrossRef Calabrese F, Molteni R, Gabriel C, Mocaer E, Racagni G, Riva MA (2011) Modulation of neuroplastic molecules in selected brain regions after chronic administration of the novel antidepressant agomelatine. Psychopharmacology 215(2):267–275. doi:10.​1007/​s00213-010-2129-8 PubMedCrossRef
go back to reference Chen Z, Zhong C (2013) Decoding Alzheimer’s disease from perturbed cerebral glucose metabolism: implications for diagnostic and therapeutic strategies. Prog Neurobiol 108:21–43PubMedCrossRef Chen Z, Zhong C (2013) Decoding Alzheimer’s disease from perturbed cerebral glucose metabolism: implications for diagnostic and therapeutic strategies. Prog Neurobiol 108:21–43PubMedCrossRef
go back to reference Correia SC, Santos RX, Perry G, Zhu X, Moreira PI, Smith MA (2011) Insulin-resistant brain state: the culprit in sporadic Alzheimer’s disease? Ageing Res Rev 10:264–273PubMedCentralPubMedCrossRef Correia SC, Santos RX, Perry G, Zhu X, Moreira PI, Smith MA (2011) Insulin-resistant brain state: the culprit in sporadic Alzheimer’s disease? Ageing Res Rev 10:264–273PubMedCentralPubMedCrossRef
go back to reference Cuervo AM, Bergamini E, Brunk UT, Dröge W, Ffrench M, Terman A (2005) Autophagy and aging: the importance of maintaining “clean” cells. Autophagy 1:131–140PubMedCrossRef Cuervo AM, Bergamini E, Brunk UT, Dröge W, Ffrench M, Terman A (2005) Autophagy and aging: the importance of maintaining “clean” cells. Autophagy 1:131–140PubMedCrossRef
go back to reference Dombrovski AY, Lenze EJ, Dew MA, Mulsant BH, Pollock BG, Houck PR, Reynolds CF 3rd (2007) Maintenance treatment for old-age depression preserves health-related quality of life: a randomized, controlled trial of paroxetine and interpersonal psychotherapy. J Am Geriatr Soc 55(9):1325–1332. doi:10.1111/j.1532-5415.2007.01292.x PubMedCrossRef Dombrovski AY, Lenze EJ, Dew MA, Mulsant BH, Pollock BG, Houck PR, Reynolds CF 3rd (2007) Maintenance treatment for old-age depression preserves health-related quality of life: a randomized, controlled trial of paroxetine and interpersonal psychotherapy. J Am Geriatr Soc 55(9):1325–1332. doi:10.​1111/​j.​1532-5415.​2007.​01292.​x PubMedCrossRef
go back to reference Epel ES (2009) Psychological and metabolic stress: a recipe for accelerated cellular aging? Hormones (Athens) 8:7–22CrossRef Epel ES (2009) Psychological and metabolic stress: a recipe for accelerated cellular aging? Hormones (Athens) 8:7–22CrossRef
go back to reference Gump BB, Matthews KA, Eberly LE, Chang YF (2005) Depressive symptoms and mortality in men: results from the multiple risk factor intervention trial. Stroke 36(1):98–102PubMedCrossRef Gump BB, Matthews KA, Eberly LE, Chang YF (2005) Depressive symptoms and mortality in men: results from the multiple risk factor intervention trial. Stroke 36(1):98–102PubMedCrossRef
go back to reference Hars ES, Qi H, Ryazanov AG, Jin S, Cai L, Hu C et al (2007) Autophagy regulates ageing in C. elegans. Autophagy 3:93–95PubMedCrossRef Hars ES, Qi H, Ryazanov AG, Jin S, Cai L, Hu C et al (2007) Autophagy regulates ageing in C. elegans. Autophagy 3:93–95PubMedCrossRef
go back to reference Haxaire C, Turpin FR, Potier B, Kervern M, Sinet PM, Barbanel G, Mothet JP, Dutar P, Billard JM (2012) Reversal of age-related oxidative stress prevents hippocampal synaptic plasticity deficits by protecting d-serine-dependent NMDA receptor activation. Aging Cell 11(2):336–344. doi:10.1111/j.1474-9726.2012.00792.x PubMedCrossRef Haxaire C, Turpin FR, Potier B, Kervern M, Sinet PM, Barbanel G, Mothet JP, Dutar P, Billard JM (2012) Reversal of age-related oxidative stress prevents hippocampal synaptic plasticity deficits by protecting d-serine-dependent NMDA receptor activation. Aging Cell 11(2):336–344. doi:10.​1111/​j.​1474-9726.​2012.​00792.​x PubMedCrossRef
go back to reference Helies JM, Diane A, Langlois A, Larue-Achagiotis C, Fromentin G, Tome D, Mormede P, Marissal-Arvy N (2005) Comparison of fat storage between Fischer 344 and obesity-resistant Lou/C rats fed different diets. Obes Res 13(1):3–10. doi:10.1038/oby.2005.3 PubMedCrossRef Helies JM, Diane A, Langlois A, Larue-Achagiotis C, Fromentin G, Tome D, Mormede P, Marissal-Arvy N (2005) Comparison of fat storage between Fischer 344 and obesity-resistant Lou/C rats fed different diets. Obes Res 13(1):3–10. doi:10.​1038/​oby.​2005.​3 PubMedCrossRef
go back to reference Kendler KS, Karkowski LM, Prescott CA (1999) Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry 156(6):837–841PubMedCrossRef Kendler KS, Karkowski LM, Prescott CA (1999) Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry 156(6):837–841PubMedCrossRef
go back to reference Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS (2003) The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 289(23):3095–3105. doi:10.1001/jama.289.23.3095 PubMedCrossRef Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS (2003) The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 289(23):3095–3105. doi:10.​1001/​jama.​289.​23.​3095 PubMedCrossRef
go back to reference Kessler RC, Birnbaum HG, Shahly V, Bromet E, Hwang I, McLaughlin KA, Sampson N, Andrade LH, de Girolamo G, Demyttenaere K, Haro JM, Karam AN, Kostyuchenko S, Kovess V, Lara C, Levinson D, Matschinger H, Nakane Y, Browne MO, Ormel J, Posada-Villa J, Sagar R, Stein DJ (2010) Age differences in the prevalence and co-morbidity of DSM-IV major depressive episodes: results from the WHO World Mental Health Survey Initiative. Depress Anxiety 27(4):351–364. doi:10.1002/da.20634 PubMedCentralPubMedCrossRef Kessler RC, Birnbaum HG, Shahly V, Bromet E, Hwang I, McLaughlin KA, Sampson N, Andrade LH, de Girolamo G, Demyttenaere K, Haro JM, Karam AN, Kostyuchenko S, Kovess V, Lara C, Levinson D, Matschinger H, Nakane Y, Browne MO, Ormel J, Posada-Villa J, Sagar R, Stein DJ (2010) Age differences in the prevalence and co-morbidity of DSM-IV major depressive episodes: results from the WHO World Mental Health Survey Initiative. Depress Anxiety 27(4):351–364. doi:10.​1002/​da.​20634 PubMedCentralPubMedCrossRef
go back to reference Ladurelle N, Gabriel C, Viggiano A, Mocaer E, Baulieu EE, Bianchi M (2012) Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC. Psychopharmacology 221(3):493–509. doi:10.1007/s00213-011-2597-5 PubMedCrossRef Ladurelle N, Gabriel C, Viggiano A, Mocaer E, Baulieu EE, Bianchi M (2012) Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC. Psychopharmacology 221(3):493–509. doi:10.​1007/​s00213-011-2597-5 PubMedCrossRef
go back to reference Lenze EJ, Schulz R, Martire LM, Zdaniuk B, Glass T, Kop WJ, Jackson SA, Reynolds CF 3rd (2005) The course of functional decline in older people with persistently elevated depressive symptoms: longitudinal findings from the cardiovascular health study. J Am Geriatr Soc 53(4):569–575. doi:10.1111/j.1532-5415.2005.53202.x PubMedCrossRef Lenze EJ, Schulz R, Martire LM, Zdaniuk B, Glass T, Kop WJ, Jackson SA, Reynolds CF 3rd (2005) The course of functional decline in older people with persistently elevated depressive symptoms: longitudinal findings from the cardiovascular health study. J Am Geriatr Soc 53(4):569–575. doi:10.​1111/​j.​1532-5415.​2005.​53202.​x PubMedCrossRef
go back to reference Li N, Liu R-J, Dwyer JM, Banasr M, Lee B, Son H, Li X-Y, Aghajanian G, Duman RS (2011) Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psych 69(8):754–761CrossRef Li N, Liu R-J, Dwyer JM, Banasr M, Lee B, Son H, Li X-Y, Aghajanian G, Duman RS (2011) Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psych 69(8):754–761CrossRef
go back to reference Lipinski MM, Zheng B, Lu T, Yan ZY, Py BF, Ng A, Xavier RJ, Li C, Yankner BA, Scherzer CR, Yuan JY (2010) Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease. Proc Natl Acad Sci US 107:14164–14169CrossRef Lipinski MM, Zheng B, Lu T, Yan ZY, Py BF, Ng A, Xavier RJ, Li C, Yankner BA, Scherzer CR, Yuan JY (2010) Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease. Proc Natl Acad Sci US 107:14164–14169CrossRef
go back to reference Luppa M, Konig HH, Heider D, Leicht H, Motzek T, Schomerus G, Riedel-Heller SG (2013) Direct costs associated with depressive symptoms in late life: a 4.5-year prospective study. Int Psychogeriatr/IPA 25(2):292–302. doi:10.1017/S1041610212001688 CrossRef Luppa M, Konig HH, Heider D, Leicht H, Motzek T, Schomerus G, Riedel-Heller SG (2013) Direct costs associated with depressive symptoms in late life: a 4.5-year prospective study. Int Psychogeriatr/IPA 25(2):292–302. doi:10.​1017/​S104161021200168​8 CrossRef
go back to reference Maheu FS, Joober R, Lupien SJ (2005) Declarative memory after stress in humans: differential involvement of the beta-adrenergic and corticosteroid systems. J Clin Endocrinol Metabol 90(3):1697–1704. doi:10.1210/jc.2004-0009 CrossRef Maheu FS, Joober R, Lupien SJ (2005) Declarative memory after stress in humans: differential involvement of the beta-adrenergic and corticosteroid systems. J Clin Endocrinol Metabol 90(3):1697–1704. doi:10.​1210/​jc.​2004-0009 CrossRef
go back to reference Marissal-Arvy N, Gaumont A, Langlois A, Dabertrand F, Bouchecareilh M, Tridon C, Mormede P (2007) Strain differences in hypothalamic pituitary adrenocortical axis function and adipogenic effects of corticosterone in rats. J Endocrinol 195(3):473–484. doi:10.1677/JOE-07-0077 PubMedCrossRef Marissal-Arvy N, Gaumont A, Langlois A, Dabertrand F, Bouchecareilh M, Tridon C, Mormede P (2007) Strain differences in hypothalamic pituitary adrenocortical axis function and adipogenic effects of corticosterone in rats. J Endocrinol 195(3):473–484. doi:10.​1677/​JOE-07-0077 PubMedCrossRef
go back to reference Marissal-Arvy N, Diane A, Moisan MP, Larue-Achagiotis C, Tridon C, Tome D, Fromentin G, Mormede P (2013) QTLs influencing carbohydrate and fat choice in a LOU/CxFischer 344 F2 rat population. Obesity (Silver Spring). doi:10.1002/oby.20485 Marissal-Arvy N, Diane A, Moisan MP, Larue-Achagiotis C, Tridon C, Tome D, Fromentin G, Mormede P (2013) QTLs influencing carbohydrate and fat choice in a LOU/CxFischer 344 F2 rat population. Obesity (Silver Spring). doi:10.​1002/​oby.​20485
go back to reference McEwen BS (2002) Sex, stress and the hippocampus: allostasis, allostatic load and the aging process. Neurobiol Aging 23(5):921–939PubMedCrossRef McEwen BS (2002) Sex, stress and the hippocampus: allostasis, allostatic load and the aging process. Neurobiol Aging 23(5):921–939PubMedCrossRef
go back to reference McIntyre RS, Soczynska JK, Konarski JZ, Woldeyohannes HO, Law CW et al (2007) Should depressive syndromes be reclassified as “metabolic syndrome type II”? Ann Clin Psychiatry 19(4):257–264PubMedCrossRef McIntyre RS, Soczynska JK, Konarski JZ, Woldeyohannes HO, Law CW et al (2007) Should depressive syndromes be reclassified as “metabolic syndrome type II”? Ann Clin Psychiatry 19(4):257–264PubMedCrossRef
go back to reference Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R, Fernandez E, Flurkey K, Javors MA, Nelson JF, Orihuela CJ, Pletcher S, Sharp ZD, Sinclair D, Starnes JW, Wilkinson JE, Nadon NL, Strong R (2011) Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J Gerontol 66(2):191–201. doi:10.1093/gerona/glq178 CrossRef Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R, Fernandez E, Flurkey K, Javors MA, Nelson JF, Orihuela CJ, Pletcher S, Sharp ZD, Sinclair D, Starnes JW, Wilkinson JE, Nadon NL, Strong R (2011) Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J Gerontol 66(2):191–201. doi:10.​1093/​gerona/​glq178 CrossRef
go back to reference Otte DM, Barcena de Arellano ML, Bilkei-Gorzo A, Albayram O, Imbeault S et al (2013) Effects of chronic d-serine elevation on animal models of depression and anxiety-related behavior. PLoS One 8(6):67131CrossRef Otte DM, Barcena de Arellano ML, Bilkei-Gorzo A, Albayram O, Imbeault S et al (2013) Effects of chronic d-serine elevation on animal models of depression and anxiety-related behavior. PLoS One 8(6):67131CrossRef
go back to reference Sapolsky RM (1999) Glucocorticoids, stress, and their adverse neurological effects: relevance to aging. Exp Gerontol 34:721–732PubMedCrossRef Sapolsky RM (1999) Glucocorticoids, stress, and their adverse neurological effects: relevance to aging. Exp Gerontol 34:721–732PubMedCrossRef
go back to reference Simonsen A, Cumming RC, Brech A, Isakson P, Schubert DR, Finley KD (2008) Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 4:176–184PubMedCrossRef Simonsen A, Cumming RC, Brech A, Isakson P, Schubert DR, Finley KD (2008) Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 4:176–184PubMedCrossRef
go back to reference Sterling P, Eyer J (1988) Allostasis: a new paradigm to explain arousal pathology. In: Fisher S, Reason J (eds) Handbook of life stress, cognition and health. Wiley, New York, pp 629–649 Sterling P, Eyer J (1988) Allostasis: a new paradigm to explain arousal pathology. In: Fisher S, Reason J (eds) Handbook of life stress, cognition and health. Wiley, New York, pp 629–649
go back to reference Swaab DF, Bao AM, Lucassen PJ (2005) The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 4(2):141–194PubMedCrossRef Swaab DF, Bao AM, Lucassen PJ (2005) The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 4(2):141–194PubMedCrossRef
go back to reference Takeda S, Sato N, Rakugi H, Morishita R (2011) Molecular mechanisms linking diabetes mellitus and Alzheimer disease: beta-amyloid peptide, insulin signaling, and neuronal function. Mol Biosyst 7:1822–1827PubMedCrossRef Takeda S, Sato N, Rakugi H, Morishita R (2011) Molecular mechanisms linking diabetes mellitus and Alzheimer disease: beta-amyloid peptide, insulin signaling, and neuronal function. Mol Biosyst 7:1822–1827PubMedCrossRef
go back to reference Tsakiri EN, Sykiotis GP, Papassideri IS, Terpos E, Dimopoulos MA, Gorgoulis VG, Bohmann D, Trougakos IP (2013) Proteasome dysfunction in Drosophila signals to an Nrf2-dependent regulatory circuit aiming to restore proteostasis and prevent premature aging. Aging Cell 12(5):802–813. doi:10.1111/acel.12111 PubMedCentralPubMedCrossRef Tsakiri EN, Sykiotis GP, Papassideri IS, Terpos E, Dimopoulos MA, Gorgoulis VG, Bohmann D, Trougakos IP (2013) Proteasome dysfunction in Drosophila signals to an Nrf2-dependent regulatory circuit aiming to restore proteostasis and prevent premature aging. Aging Cell 12(5):802–813. doi:10.​1111/​acel.​12111 PubMedCentralPubMedCrossRef
go back to reference Vachon-Presseau E, Roy M, Martel MO, Caron E, Marin MF, Chen J, Albouy G, Plante I, Sullivan MJ, Lupien SJ, Rainville P (2013) The stress model of chronic pain: evidence from basal cortisol and hippocampal structure and function in humans. Brain 136(Pt 3):815–827. doi:10.1093/brain/aws371 PubMedCrossRef Vachon-Presseau E, Roy M, Martel MO, Caron E, Marin MF, Chen J, Albouy G, Plante I, Sullivan MJ, Lupien SJ, Rainville P (2013) The stress model of chronic pain: evidence from basal cortisol and hippocampal structure and function in humans. Brain 136(Pt 3):815–827. doi:10.​1093/​brain/​aws371 PubMedCrossRef
go back to reference Verhoeven JE, Révész D, Epel ES, Lin J, Wolkowitz OM, Penninx BW (2013) Major depressive disorder and accelerated cellular aging: results from a large psychiatric cohort study. Mol Psychiatry. doi:10.1038/mp.2013.151 PubMedCentral Verhoeven JE, Révész D, Epel ES, Lin J, Wolkowitz OM, Penninx BW (2013) Major depressive disorder and accelerated cellular aging: results from a large psychiatric cohort study. Mol Psychiatry. doi:10.​1038/​mp.​2013.​151 PubMedCentral
go back to reference Watson GS, Craft S (2004) Modulation of memory by insulin and glucose: neuropsychological observations in Alzheimer’s disease. Eur J Pharmacol 490:97–113PubMedCrossRef Watson GS, Craft S (2004) Modulation of memory by insulin and glucose: neuropsychological observations in Alzheimer’s disease. Eur J Pharmacol 490:97–113PubMedCrossRef
go back to reference Zarate C, Singh J, Manji HK (2006) Cellular plasticity cascades: targets for the development of novel therapeutics for bipolar disorder. Biol Psych 59:1006–1020CrossRef Zarate C, Singh J, Manji HK (2006) Cellular plasticity cascades: targets for the development of novel therapeutics for bipolar disorder. Biol Psych 59:1006–1020CrossRef
Metadata
Title
Mechanisms underlying the neuroprotective effect of brain reserve against late life depression
Authors
Thomas Freret
Pierrette Gaudreau
Pascale Schumann-Bard
Jean-Marie Billard
Aurel Popa-Wagner
Publication date
01-08-2015
Publisher
Springer Vienna
Published in
Journal of Neural Transmission / Issue Special Issue 1/2015
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI
https://doi.org/10.1007/s00702-013-1154-2

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