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Current Drug Targets


ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Review Article

Navigating Alzheimer’s Disease via Chronic Stress: The Role of Glucocorticoids

Author(s): Vivek Kumar Sharma and Thakur Gurjeet Singh*

Volume 21 , Issue 5 , 2020

Page: [433 - 444] Pages: 12

DOI: 10.2174/1389450120666191017114735

Price: $65


Alzheimer’s disease (AD) is a chronic intensifying incurable progressive disease leading to neurological deterioration manifested as impairment of memory and executive brain functioning affecting the physical ability like intellectual brilliance, common sense in patients. The recent therapeutic approach in Alzheimer's disease is only the symptomatic relief further emerging the need for therapeutic strategies to be targeted in managing the underlying silent killing progression of dreaded pathology. Therefore, the current research direction is focused on identifying the molecular mechanisms leading to the evolution of the understanding of the neuropathology of Alzheimer's disease. The resultant saturation in the area of current targets (amyloid β, τ Protein, oxidative stress etc.) has led the scientific community to rethink of the mechanistic neurodegenerative pathways and reprogram the current research directions. Although, the role of stress has been recognized for many years and contributing to the development of cognitive impairment, the area of stress has got the much-needed impetus recently and is being recognized as a modifiable menace for AD. Stress is an unavoidable human experience that can be resolved and normalized but chronic activation of stress pathways unsettle the physiological status. Chronic stress mediated activation of neuroendocrine stimulation is generally linked to a high risk of developing AD. Chronic stress-driven physiological dysregulation and hypercortisolemia intermingle at the neuronal level and leads to functional (hypometabolism, excitotoxicity, inflammation) and anatomical remodeling of the brain architecture (senile plaques, τ tangles, hippocampal atrophy, retraction of spines) ending with severe cognitive deterioration. The present review is an effort to collect the most pertinent evidence that support chronic stress as a realistic and modifiable therapeutic earmark for AD and to advocate glucocorticoid receptors as therapeutic interventions.

Keywords: Stress, glucocorticoids, HPA axis, Alzheimer's disease, inflammation, amyloid β, neurodegeneration.

Graphical Abstract
Sanabria-Castro A, Alvarado-Echeverría I, Monge-Bonilla C. Molecular pathogenesis of alzheimer’s disease: An Update. Ann Neurosci 2017; 24(1): 46-54.
[] [PMID: 28588356]
Iqbal K, Grundke-Iqbal I. Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention. J Cell Mol Med 2008; 12(1): 38-55.
[] [PMID: 18194444]
Matos TM, Souza-Talarico JN. How stress mediators can cumulatively contribute to Alzheimer’s disease an allostatic load approach. Dement Neuropsychol 2019; 13(1): 11-21.
[] [PMID: 31073376]
Sotiropoulos I, Catania C, Pinto LG, et al. Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits. J Neurosci 2011; 31(21): 7840-7.
[] [PMID: 21613497]
Canet G, Chevallier N, Perrier V, Desrumaux C, Givalois L. Targeting glucocorticoid receptors: a new avenue for alzheimer’s disease therapy pathology, prevention and therapeutics of neurodegenerative disease. Singapore: Springer 2019.
Fedotova J, Soultanov V, Nikitina T, Roschin V, Ordyan N, Hritcu L. Cognitive-enhancing activities of the polyprenol preparation Ropren® in gonadectomized β-amyloid (25-35) rat model of Alzheimer’s disease. Physiol Behav 2016; 157: 55-62.
[] [PMID: 26821186]
Stein-Behrens B, Mattson MP, Chang I, Yeh M, Sapolsky R. Stress exacerbates neuron loss and cytoskeletal pathology in the hippocampus. J Neurosci 1994; 14(9): 5373-80.
[] [PMID: 8083742]
Pariante CM, Lightman SL. The HPA axis in major depression: classical theories and new developments. Trends Neurosci 2008; 31(9): 464-8.
[] [PMID: 18675469]
Canet G, Chevallier N, Zussy C, Desrumaux C, Givalois L. Central role of glucocorticoids receptors in Alzheimer’s disease and depression. Front Neurosci 2018; 12: 739.
[] [PMID: 30459541]
Sapolsky RM, Krey LC, McEwen BS. Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging. J Neurosci 1985; 5(5): 1222-7.
[] [PMID: 3998818]
Swaab DF, Raadsheer FC, Endert E, Hofman MA, Kamphorst W, Ravid R. Increased cortisol levels in aging and Alzheimer’s disease in postmortem cerebrospinal fluid. J Neuroendocrinol 1994; 6(6): 681-7.
[] [PMID: 7894471]
Bisht K, Sharma K, Tremblay MÈ. Chronic stress as a risk factor for Alzheimer’s disease: Roles of microglia-mediated synaptic remodeling, inflammation, and oxidative stress. Neurobiol Stress 2018; 9: 9-21.
[] [PMID: 29992181]
Notarianni E. Cortisol: Mediator of association between Alzheimer’s disease and diabetes mellitus? Psychoneuroendocrinology 2017; 81: 129-37.
[] [PMID: 28458232]
Ahmad MH, Fatima M, Mondal AC. Role of hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis and insulin signaling in the pathophysiology of alzheimer’s disease. Neuropsychobiology 2019; 77(4): 197-205.
Ouanes S, Popp J. High cortisol and the risk of dementia and alzheimer’s disease: a review of the literature. Front Aging Neurosci 2019; 11: 43.
[] [PMID: 30881301]
Roozendaal B. 1999 Curt P. Richter award. Glucocorticoids and the regulation of memory consolidation. Psychoneuroendocrinology 2000; 25(3): 213-38.
[] [PMID: 10737694]
McEwen BS. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev 2007; 87(3): 873-904.
[] [PMID: 17615391]
Lupien SJ, Maheu F, Tu M, Fiocco A, Schramek TE. The effects of stress and stress hormones on human cognition: Implications for the field of brain and cognition. Brain Cogn 2007; 65(3): 209-37.
[] [PMID: 17466428]
Gray JD, Kogan JF, Marrocco J, McEwen BS. Genomic and epigenomic mechanisms of glucocorticoids in the brain. Nat Rev Endocrinol 2017; 13(11): 661-73.
[] [PMID: 28862266]
Fuchs E, Czéh B, Kole MHP, Michaelis T, Lucassen PJ. Alterations of neuroplasticity in depression: the hippocampus and beyond. Eur Neuropsychopharmacol 2004; 14(Suppl. 5): S481-90.
[] [PMID: 15550346]
Swaab DF, Bao AM, Lucassen PJ. The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 2005; 4(2): 141-94.
[] [PMID: 15996533]
Vyas A, Pillai AG, Chattarji S. Recovery after chronic stress fails to reverse amygdaloid neuronal hypertrophy and enhanced anxiety-like behavior. Neuroscience 2004; 128(4): 667-73.
[] [PMID: 15464275]
McEwen BS. Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol 2008; 583(2-3): 174-85.
[] [PMID: 18282566]
Thal DR, Rüb U, Orantes M, Braak H. Phases of A β-deposition in the human brain and its relevance for the development of AD. Neurology 2002; 58(12): 1791-800.
[] [PMID: 12084879]
Machado A, Herrera AJ, de Pablos RM, et al. Chronic stress as a risk factor for Alzheimer’s disease. Rev Neurosci 2014; 25(6): 785-804.
[] [PMID: 25178904]
Kathryn M. The Effect of Glucocorticoid and Glucocorticoid Receptor Interactions on Brain, Spinal Cord, and Glial Cell Plasticity. Neural Plasticity 2017; Article ID 8640970, 8 pages.
de Kloet ER, Van Acker SA, Sibug RM, et al. Brain mineralocorticoid receptors and centrally regulated functions. Kidney Int 2000; 57(4): 1329-36.
[] [PMID: 10760063]
Oakley RH, Cidlowski JA. The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease. J Allergy Clin Immunol 2013; 132(5): 1033-44.
[] [PMID: 24084075]
Vyas S, Rodrigues AJ, Silva JM, et al. Chronic stress and glucocorticoids: from neuronal plasticity to neurodegeneration. Neural Plast 2016.20166391686
[] [PMID: 27034847]
Dioli C, Patrício P, Sousa N, et al. Chronic stress triggers divergent dendritic alterations in immature neurons of the adult hippocampus, depending on their ultimate terminal fields. Transl Psychiatry 2019; 9(1): 143.
[] [PMID: 31028242]
Yan Y, Dominguez S, Fisher DW, Dong H. Sex differences in chronic stress responses and Alzheimer’s disease. Neurobiol Stress 2018; 8: 120-6.
[] [PMID: 29888307]
McEwen BS. The neurobiology of stress: from serendipity to clinical relevance. Brain Res 2000; 886(1-2): 172-89.
[] [PMID: 11119695]
Lanté F, Chafai M, Raymond EF, et al. Subchronic glucocorticoid receptor inhibition rescues early episodic memory and synaptic plasticity deficits in a mouse model of Alzheimer’s disease. Neuropsychopharmacology 2015; 40(7): 1772-81.
[] [PMID: 25622751]
Lewerenz J, Maher P. chronic glutamate toxicity in neurodegenerative diseases-what is the evidence? Front Neurosci 2015; 9: 469.
[] [PMID: 26733784]
Tu S, Okamoto S, Lipton SA, Xu H. Oligomeric Aβ-induced synaptic dysfunction in Alzheimer’s disease. Mol Neurodegener 2014; 9: 48.
[] [PMID: 25394486]
Mravec B, Horvathova L, Padova A. Brain under Stress and Alzheimer’s disease. Cell Mol Neurobiol 2018; 38(1): 73-84.
[] [PMID: 28699112]
Popoli M, Yan Z, McEwen BS, Sanacora G. The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nat Rev Neurosci 2011; 13(1): 22-37.
[] [PMID: 22127301]
Jauregui-Huerta F, Ruvalcaba-Delgadillo Y, Gonzalez-Castañeda R, Garcia-Estrada J, Gonzalez-Perez O, Luquin S. Responses of glial cells to stress and glucocorticoids. Curr Immunol Rev 2010; 6(3): 195-204.
[] [PMID: 20729991]
Sahlender DA, Savtchouk I, Volterra A. What do we know about gliotransmitter release from astrocytes? Philos Trans R Soc Lond B Biol Sci 2014; 369(1654)20130592
[] [PMID: 25225086]
Pearson-Leary J, Osborne DM, McNay EC. Role of glia in stressinduced enhancement and impairment of memory. Front Integr Neurosci 2016; 11: 9: 63.
Acuña D, Fernández B, Gomar MD, del Aguila CM, Castillo JL. Influence of the pituitary-adrenal axis on benzodiazepine receptor binding to rat cerebral cortex. Neuroendocrinology 1990; 51(1): 97-103.
[] [PMID: 2154713]
Zeise ML, Madamba S, Siggins GR. Interleukin-1 beta increases synaptic inhibition in rat hippocampal pyramidal neurons in vitro. Regul Pept 1992; 39(1): 1-7.
[] [PMID: 1579655]
Abrahám IM, Meerlo P, Luiten PG. Concentration dependent actions of glucocorticoids on neuronal viability and survival. Dose Response 2006; 4(1): 38-54.
[] [PMID: 18648635]
Merchenthaler I, Vigh S, Petrusz P, Schally AV. Immunocytochemical localization of corticotropin-releasing factor (CRF) in the rat brain. Am J Anat 1982; 165(4): 385-96.
[] [PMID: 6760710]
Henckens MJ, Deussing JM, Chen A. Region-specific roles of the corticotropin-releasing factor-urocortin system in stress. Nat Rev Neurosci 2016; 17(10): 636-51.
[] [PMID: 27586075]
Thathiah A, De Strooper B. The role of G protein-coupled receptors in the pathology of Alzheimer’s disease. Nat Rev Neurosci 2011; 12(2): 73-87.
[] [PMID: 21248787]
Park HJ, Ran Y, Jung JI, et al. The stress response neuropeptide CRF increases amyloid-β production by regulating γ-secretase activity. EMBO J 2015; 34(12): 1674-86.
[] [PMID: 25964433]
Willem M, Tahirovic S, Busche MA, et al. η-Secretase processing of APP inhibits neuronal activity in the hippocampus. Nature 2015; 526(7573): 443-7.
[] [PMID: 26322584]
Ishijima S, Baba H, Maeshima H, et al. Glucocorticoid may influence amyloid β metabolism in patients with depression. Psychiatry Res 2018; 259: 191-6.
[] [PMID: 29073556]
Lahiri DK. Functional characterization of amyloid beta precursor protein regulatory elements: rationale for the identification of genetic polymorphism. Ann N Y Acad Sci 2004; 1030: 282-8.
[] [PMID: 15659808]
Sambamurti K, Kinsey R, Maloney B, Ge YW, Lahiri DK. Gene structure and organization of the human beta-secretase (BACE) promoter. FASEB J 2004; 18(9): 1034-6.
[] [PMID: 15059975]
Kim N. Green, Lauren M. Billings, Benno Roozendaal, James L. McGaugh, and Frank M. LaFerla; Glucocortiocoids and hyperphosphyorylation of Tau mGlucocorticoids increase amyloid-β and Tau pathology in a mouse model of Alzheimer’s disease. J Neurosci 2006; 26(35): 9047-56.
[] [PMID: 16943563]
Briones TL, Darwish H. Decrease in age-related tau hyperphosphorylation and cognitive improvement following vitamin D supplementation are associated with modulation of brain energy metabolism and redox state. Neuroscience 2014; 262: 143-55.
[] [PMID: 24412233]
Dehmelt L, Halpain S. The MAP2/Tau family of microtubule-associated proteins. Genome Biol 2005; 6(1): 204.
[] [PMID: 15642108]
Frost B, Hemberg M, Lewis J, Feany MB. Tau promotes neurodegeneration through global chromatin relaxation. Nat Neurosci 2014; 17(3): 357-66.
[] [PMID: 24464041]
Hashiguchi M, Hashiguchi T. Kinase-kinase interaction and modulation of tau phosphorylation. Int Rev Cell Mol Biol 2013; 300: 121-60.
[] [PMID: 23273861]
Götz J, Xia D, Leinenga G, Chew YL, Nicholas H. What renders TAU toxic? Front Neurol 2013; 4: 72.
[] [PMID: 23772223]
Sotiropoulos I, Catania C, Pinto LG, et al. Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits. J Neurosci 2011; 31(21): 7840-7.
[] [PMID: 21613497]
Sotiropoulos I, Silva J, Kimura T, et al. Female hippocampus vulnerability to environmental stress, a precipitating factor in Tau aggregation pathology. J Alzheimers Dis 2015; 43(3): 763-74.
[] [PMID: 25159665]
de Calignon A, Polydoro M, Suárez-Calvet M, et al. Propagation of tau pathology in a model of early Alzheimer’s disease. Neuron 2012; 73(4): 685-97.
[] [PMID: 22365544]
Dong H, Csernansky JG. Effects of stress and stress hormones on amyloid-beta protein and plaque deposition. J Alzheimers Dis 2009; 18(2): 459-69.
[] [PMID: 19584430]
Lucassen PJ, Pruessner J, Sousa N, et al. Neuropathology of stress. Acta Neuropathol 2014; 127(1): 109-35.
[] [PMID: 24318124]
You JM, Yun SJ, Nam KN, Kang C, Won R, Lee EH. Mechanism of glucocorticoid-induced oxidative stress in rat hippocampal slice cultures. Can J Physiol Pharmacol 2009; 87(6): 440-7.
[] [PMID: 19526038]
Suri D, Vaidya VA. Glucocorticoid regulation of brain-derived neurotrophic factor: relevance to hippocampal structural and functional plasticity. Neuroscience 2013; 239: 196-213.
[] [PMID: 22967840]
Hock C, Heese K, Hulette C, Rosenberg C, Otten U. Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas. Arch Neurol 2000; 57(6): 846-51.
[] [PMID: 10867782]
Nagahara AH, Merrill DA, Coppola G, et al. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease. Nat Med 2009; 15(3): 331-7.
[] [PMID: 19198615]
Li S, Wang C, Wang W, Dong H, Hou P, Tang Y. Chronic mild stress impairs cognition in mice: from brain homeostasis to behavior. Life Sci 2008; 82(17-18): 934-42.
[] [PMID: 18402983]
Sapolsky RM. Stress, the Aging Brain, and the Mechanisms of Neuron Death. Cambridge, Massachusetts: MIT Press 1992.
Conrad CD. What is the functional significance of chronic stress-induced CA3 dendritic retraction within the hippocampus? Behav Cogn Neurosci Rev 2006; 5(1): 41-60.
[] [PMID: 16816092]
Li WZ, Li WP, Yao YY, et al. Glucocorticoids increase impairments in learning and memory due to elevated amyloid precursor protein expression and neuronal apoptosis in 12-month old mice. Eur J Pharmacol 2010; 628(1-3): 108-15.
[] [PMID: 19948164]
Meier-Ruge W, Bertoni-Freddari C. The significance of glucose turnover in the brain in the pathogenetic mechanisms of Alzheimer’s disease. Rev Neurosci 1996; 7(1): 1-19.
[] [PMID: 8736675]
Rothman SM, Mattson MP. Adverse stress, hippocampal networks, and Alzheimer’s disease. Neuromolecular Med 2010; 12(1): 56-70.
[] [PMID: 19943124]
Levone BR, Cryan JF, O’Leary OF. Role of adult hippocampal neurogenesis in stress resilience. Neurobiol Stress 2014; 1: 147-55.
[] [PMID: 27589664]
Kim JJ, Diamond DM. The stressed hippocampus, synaptic plasticity and lost memories. Nat Rev Neurosci 2002; 3(6): 453-62.
[] [PMID: 12042880]
Lyman M, Lloyd DG, Ji X, Vizcaychipi MP, Ma D. Neuroinflammation: the role and consequences. Neurosci Res 2014; 79: 1-12.
[] [PMID: 24144733]
Gasteiger G, Rudensky AY. Interactions between innate and adaptive lymphocytes. Nat Rev Immunol 2014; 14(9): 631-9.
[] [PMID: 25132095]
Schaefer L. Complexity of danger: the diverse nature of damage-associated molecular patterns. J Biol Chem 2014; 289(51): 35237-45.
[] [PMID: 25391648]
Jope RS, Cheng Y, Lowell JA, Worthen RJ, Sitbon YH, Beurel E. Stressed and inflamed, can GSK3 be blamed? Trends Biochem Sci 2017; 42(3): 180-92.
[] [PMID: 27876551]
De Martinis M, Sirufo MM, Ginaldi L. Raynaud’s phenomenon and nailfold capillaroscopic findings in anorexia nervosa. Curr Med Res Opin 2018; 34(3): 547-50.
[] [PMID: 29292666]
Ciccarelli F, De Martinis M, Ginaldi L. Glucocorticoids in patients with rheumatic diseases: friends or enemies of bone? Curr Med Chem 2015; 22(5): 596-603.
[] [PMID: 25386817]
Madrigal JL, Hurtado O, Moro MA, et al. The increase in TNF-alpha levels is implicated in NF-kappaB activation and inducible nitric oxide synthase expression in brain cortex after immobilization stress. Neuropsychopharmacology 2002; 26(2): 155-63.
[] [PMID: 11790511]
Toussay X, Basu K, Lacoste B, Hamel E. Locus coeruleus stimulation recruits a broad cortical neuronal network and increases cortical perfusion. J Neurosci 2013; 33(8): 3390-401.
[] [PMID: 23426667]
Robertson SD, Plummer NW, de Marchena J, Jensen P. Developmental origins of central norepinephrine neuron diversity. Nat Neurosci 2013; 16(8): 1016-23.
[] [PMID: 23852112]
Mravec B, Lejavova K, Cubinkova V. Locus (coeruleus) minoris resistentiae in pathogenesis of Alzheimer’s disease. Curr Alzheimer Res 2014; 11(10): 992-1001.
[] [PMID: 25387337]
Swanson LW, Hartman BK. The central adrenergic system. An immunofluorescence study of the location of cell bodies and their efferent connections in the rat utilizing dopamine-beta-hydroxylase as a marker. J Comp Neurol 1975; 163(4): 467-505.
[] [PMID: 1100685]
Tully K, Bolshakov VY. Emotional enhancement of memory: how norepinephrine enables synaptic plasticity. Mol Brain 2010; 3: 15.
[] [PMID: 20465834]
O’Donnell J, Zeppenfeld D, McConnell E, Pena S, Nedergaard M. Norepinephrine: a neuromodulator that boosts the function of multiple cell types to optimize CNS performance. Neurochem Res 2012; 37(11): 2496-512.
[] [PMID: 22717696]
Morris KA, Chang Q, Mohler EG, Gold PE. Age-related memory impairments due to reduced blood glucose responses to epinephrine. Neurobiol Aging 2010; 31(12): 2136-45.
[] [PMID: 19178987]
Weidling I, Swerdlow RH. Mitochondrial dysfunction and stress responses in Alzheimer’s disease. Biology (Basel) 2019; 8: 39-47.
Rapoport SI. In vivo PET imaging and postmortem studies suggest potentially reversible and irreversible stages of brain metabolic failure in Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 1999; 249(3)(Suppl. 3): 46-55.
[] [PMID: 10654100]
Yasuno F, Imamura T, Hirono N, et al. Age at onset and regional cerebral glucose metabolism in Alzheimer’s disease. Dement Geriatr Cogn Disord 1998; 9(2): 63-7.
[] [PMID: 9524795]
Berent S, Giordani B, Foster N, et al. Neuropsychological function and cerebral glucose utilization in isolated memory impairment and Alzheimer’s disease. J Psychiatr Res 1999; 33(1): 7-16.
[] [PMID: 10094234]
Meguro K, LeMestric C, Landeau B, Desgranges B, Eustache F, Baron JC. Relations between hypometabolism in the posterior association neocortex and hippocampal atrophy in Alzheimer’s disease: a PET/MRI correlative study. J Neurol Neurosurg Psychiatry 2001; 71(3): 315-21.
[] [PMID: 11511703]
Piroli GG, Grillo CA, Reznikov LR, et al. Corticosterone impairs insulin-stimulated translocation of GLUT4 in the rat hippocampus. Neuroendocrinology 2007; 85(2): 71-80.
[] [PMID: 17426391]
Brunetti A, Fulham MJ, Aloj L, et al. Decreased brain glucose utilization in patients with Cushing’s disease. J Nucl Med 1998; 39(5): 786-90.
[PMID: 9591575]
Virgin CE Jr, Ha TP, Packan DR, et al. Glucocorticoids inhibit glucose transport and glutamate uptake in hippocampal astrocytes: implications for glucocorticoid neurotoxicity. J Neurochem 1991; 57(4): 1422-8.
[] [PMID: 1680166]
Landgraf R, Mitro A, Hess J. Regional net uptake of 14C-glucose by rat brain under the influence of corticosterone. Endocrinol Exp 1978; 12(2): 119-29.
[PMID: 311731]
Amatruda JM, Livingston JN, Lockwood DH. Cellular mechanisms in selected states of insulin resistance: human obesity, glucocorticoid excess, and chronic renal failure. Diabetes Metab Rev 1985; 1(3): 293-317.
[] [PMID: 3915256]
Lambillotte C, Gilon P, Henquin JC. Direct glucocorticoid inhibition of insulin secretion. An in vitro study of dexamethasone effects in mouse islets. J Clin Invest 1997; 99(3): 414-23.
[] [PMID: 9022074]
Sapolsky RM, Krey LC, McEwen BS. Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response. Proc Natl Acad Sci USA 1984; 81(19): 6174-7.
[] [PMID: 6592609]
Roy M, Sapolsky RM. The exacerbation of hippocampal excitotoxicity by glucocorticoids is not mediated by apoptosis. Neuroendocrinology 2003; 77(1): 24-31.
[] [PMID: 12624538]
Abrahám IM, Harkany T, Horvath KM, Luiten PGM. Action of glucocorticoids on survival of nerve cells: promoting neurodegeneration or neuroprotection? J Neuroendocrinol 2001; 13(9): 749-60.
[] [PMID: 11578524]
Flannery PJ, Trushina E. Mitochondrial dynamics and transport in Alzheimer’s disease. Mol Cell Neurosci 2019; 98: 109-20.
[] [PMID: 31216425]
Hoffmann A, Spengler D. The mitochondrion as potential interface in early-life stress brain programming. Front Behav Neurosci 2018; 12: 306.
[] [PMID: 30574076]
Swerdlow RH. Mitochondria and mitochondrial cascades in Alzheimer’s disease. J Alzheimers Dis 2018; 62(3): 1403-16.
[] [PMID: 29036828]
Tönnies E, Trushina E. Oxidative stress, synaptic dysfunction, and Alzheimer’s disease. J Alzheimers Dis 2017; 57(4): 1105-21.
[] [PMID: 28059794]
Flannery PJ, Trushina E. Mitochondrial dynamics and transport in Alzheimer’s disease. Mol Cell Neurosci 2019; 98: 109-20.
[] [PMID: 31216425]
Hawkins KE, Duchen M. Modelling mitochondrial dysfunction in Alzheimer’s disease using human induced pluripotent stem cells. World J Stem Cells 2019; 11(5): 236-53.
[] [PMID: 31171953]
Hunter RG, Seligsohn M, Rubin TG, et al. Stress and corticosteroids regulate rat hippocampal mitochondrial DNA gene expression via the glucocorticoid receptor. Proc Natl Acad Sci USA 2016; 113(32): 9099-104.
[] [PMID: 27457949]
Picard M, McEwen BS. Psychological stress and mitochondria: a conceptual framework. Psychosom Med 2018; 80(2): 126-40.
[] [PMID: 29389735]
Psarra AMG, Sekeris CE. Steroid and thyroid hormone receptors in mitochondria. IUBMB Life 2008; 60(4): 210-23.
[] [PMID: 18344181]
Picard M, McEwen BS, Epel ES, Sandi C. An energetic view of stress: Focus on mitochondria. Front Neuroendocrinol 2018; 49: 72-85.
[] [PMID: 29339091]
Gong Y, Chai Y, Ding JH, Sun XL, Hu G. Chronic mild stress damages mitochondrial ultrastructure and function in mouse brain. Neurosci Lett 2011; 488(1): 76-80.
[] [PMID: 21070835]
Alageel A, Tomasi J, Tersigni C, et al. Evidence supporting a mechanistic role of sirtuins in mood and metabolic disorders. Prog Neuropsychopharmacol Biol Psychiatry 2018; 86: 95-101.
[] [PMID: 29802856]
Lapp HE, Bartlett AA, Hunter RG. Stress and glucocorticoid receptor regulation of mitochondrial gene expression. J Mol Endocrinol 2019; 62(2): R121-8.
[] [PMID: 30082335]
Kumar K, Kumar A, Keegan RM, Deshmukh R. Recent advances in the neurobiology and neuropharmacology of Alzheimer’s disease. Biomed Pharmacother 2018; 98: 297-307.
[] [PMID: 29274586]
Siddiqui MF, Levey AI. Cholinergic therapies in Alzheimer’s disease. Drugs Future 1999; 24: 417-44.
Finkelstein Y, Koffler B, Rabey JM, Gilad GM. Dynamics of cholinergic synaptic mechanisms in rat hippocampus after stress. Brain Res 1985; 343(2): 314-9.
[] [PMID: 4052753]
Paul S, Jeon WK, Bizon JL, Han J-S. Interaction of basal forebrain cholinergic neurons with the glucocorticoid system in stress regulation and cognitive impairment. Front Aging Neurosci 2015; 7: 43.
[] [PMID: 25883567]
Sapolsky RM. Glucocorticoids, and damage to the nervous system: the current state of confusion. Stress 1996; 1(1): 1-19.
Hörtnagl H, Berger ML, Havelec L, Hornykiewicz O. Role of glucocorticoids in the cholinergic degeneration in rat hippocampus induced by ethylcholine aziridinium (AF64A). J Neurosci 1993; 13(7): 2939-45.
[] [PMID: 7687281]
Paul S, Jeon WK, Bizon JL, Han J-S. Interaction of basal forebrain cholinergic neurons with the glucocorticoid system in stress regulation and cognitive impairment. Front Aging Neurosci 2015; 7: 43.
[] [PMID: 25883567]
Karran E, De Strooper B. The amyloid cascade hypothesis: are we poised for success or failure? J Neurochem 2016; 139(2)(Suppl. 2): 237-52.
[] [PMID: 27255958]
Loera-Valencia R, Piras A, Ismail MAM, et al. Targeting Alzheimer’s disease with gene and cell therapies. J Intern Med 2018; 284(1): 2-36.
[] [PMID: 29582495]
Kemppainen N, Johansson J, Teuho J, et al. Brain amyloid load and its associations with cognition and vascular risk factors in FINGER Study. Neurology 2018; 90(3): e206-13.
[] [PMID: 29263220]
Fiore R, Khudayberdiev S, Saba R, Schratt G. MicroRNA function in the nervous system. Prog Mol Biol Transl Sci 2011; 102: 47-100.
[] [PMID: 21846569]
Esteller M. Non-coding RNAs in human disease. Nat Rev Genet 2011; 12(12): 861-74.
[] [PMID: 22094949]
Yonas MA, Lange NE, Celedón JC. Psychosocial stress and asthma morbidity. Curr Opin Allergy Clin Immunol 2012; 12(2): 202-10.
[] [PMID: 22266773]
Leung AKL, Sharp PA. MicroRNA functions in stress responses. Mol Cell 2010; 40(2): 205-15.
[] [PMID: 20965416]
Turner JD, Alt SR, Cao L, et al. Transcriptional control of the glucocorticoid receptor: CpG islands, epigenetics and more. Biochem Pharmacol 2010; 15; 80(12): 1860-8.
Uchida S, Nishida A, Hara K, et al. Characterization of the vulnerability to repeated stress in Fischer 344 rats: possible involvement of microRNA-mediated down-regulation of the glucocorticoid receptor. Eur J Neurosci 2008; 27(9): 2250-61.
[] [PMID: 18445216]
Meerson A, Cacheaux L, Goosens KA, Sapolsky RM, Soreq H, Kaufer D. Changes in brain MicroRNAs contribute to cholinergic stress reactions. J Mol Neurosci 2010; 40(1-2): 47-55.
[] [PMID: 19711202]
Hunter RG. Epigenetic effects of stress and corticosteroids in the brain. Front Cell Neurosci 2012; 6: 18.
[] [PMID: 22529779]
Zannas AS, Arloth J, Carrillo-Roa T, et al. Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling. Genome Biol 2015; 16: 266.
[] [PMID: 26673150]

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