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Adult Hippocampal Neurogenesis in Major Depressive Disorder and Alzheimer’s Disease

神经发生 海马结构 疾病 神经科学 海马体 阿尔茨海默病 医学 精神科 心理学 内科学
作者
Thomas Berger,Hyun Ah Lee,Allan H. Young,Dag Aarsland,Sandrine Thuret
出处
期刊:Trends in Molecular Medicine [Elsevier BV]
卷期号:26 (9): 803-818 被引量:205
标识
DOI:10.1016/j.molmed.2020.03.010
摘要

Human AHN is severely depleted in both MDD and AD indicated by reduction of distinct neurogenic markers and hippocampal volume. Human AHN might be a converging mechanism for MDD and AD, indicating clinical as well as genetic links. Human AHN might display an interesting therapeutic target to potentially develop novel treatment strategies for MDD and AD. Depression and dementia are major public health problems. Major depressive disorder (MDD) and Alzheimer’s disease (AD) reciprocally elevate the risk for one another. No effective drug is available to treat AD and about one-third of depressive patients show treatment resistance. The biological connection between MDD and AD is still unclear. Uncovering this link might open novel ways of treatment and prevention to improve patient healthcare. Here, we discuss recent studies specifically on the role of human adult hippocampal neurogenesis (AHN) in MDD and AD. We compare diverse approaches to analyse the effect of MDD and AD on human AHN and analyse different studies implicating the role of human AHN as a potential converging mechanism in MDD and AD. Depression and dementia are major public health problems. Major depressive disorder (MDD) and Alzheimer’s disease (AD) reciprocally elevate the risk for one another. No effective drug is available to treat AD and about one-third of depressive patients show treatment resistance. The biological connection between MDD and AD is still unclear. Uncovering this link might open novel ways of treatment and prevention to improve patient healthcare. Here, we discuss recent studies specifically on the role of human adult hippocampal neurogenesis (AHN) in MDD and AD. We compare diverse approaches to analyse the effect of MDD and AD on human AHN and analyse different studies implicating the role of human AHN as a potential converging mechanism in MDD and AD. microtubule component encoded by TUBB3 gene, which is almost exclusively expressed in neurons [80.Gatt A. et al.Expression of neurogenic markers in Alzheimer’s disease: a systematic review and metatranscriptional analysis.Neurobiol. Aging. 2019; 76: 166-180Crossref PubMed Scopus (4) Google Scholar]. classification of AD severity according to the progressive spreading of neurofibrillary tangles formed by Tau. The early stages (I/II) refer to pathology which is mainly confined to transentorhinal brain regions. In stages III and IV, the hippocampus and other parts of the limbic system are affected. In stages V and VI, pathology has spread to the neocortex [81.Braak H. Braak E. Neuropathological stageing of Alzheimer-related changes.Acta Neuropathol. (Berl.). 1991; 82: 239-259Crossref PubMed Google Scholar]. as it is incorporated into cellular DNA during division, a BrdU-positive cell would have divided after BrdU administration. Often used to measure cell proliferation in hippocampus [82.Leif R.C. et al.A short history of the initial application of anti–5-BrdU to the detection and measurement of S phase.Cytometry A. 2004; 58A: 45-52Crossref Google Scholar]. birth-dating method using carbon isotope. 14C is taken up in cells and is integrated into newly synthesised DNA during cell division. The 14C amount in a cell is dependent on the concentration at the time of the cell division. Presence of different 14C levels in GN DNA demonstrated that new GNs are generated during adulthood. a calcium-binding protein and marker of mature GNs [80.Gatt A. et al.Expression of neurogenic markers in Alzheimer’s disease: a systematic review and metatranscriptional analysis.Neurobiol. Aging. 2019; 76: 166-180Crossref PubMed Scopus (4) Google Scholar]. concept that accounts for the brain’s ability to tolerate or adapt to changes before showing signs of cognitive impairment [83.Stern Y. Cognitive reserve in ageing and Alzheimer’s disease.Lancet Neurol. 2012; 11: 1006-1012Abstract Full Text Full Text PDF PubMed Scopus (846) Google Scholar]. is a microtubule-associated protein expressed in immature neurons and neural progenitor cells [80.Gatt A. et al.Expression of neurogenic markers in Alzheimer’s disease: a systematic review and metatranscriptional analysis.Neurobiol. Aging. 2019; 76: 166-180Crossref PubMed Scopus (4) Google Scholar]. includes physical abuse, emotional or psychological abuse, or child neglect [84.Brown A. et al.Bridging basic and clinical research in early life adversity, DNA methylation, and major depressive disorder.Front. Genet. 2019; 10: 229Crossref PubMed Scopus (4) Google Scholar]. Stress or trauma early in life are large risk factors for depression. application of small controlled seizures to the brain to improve symptoms in several psychiatric disorders (e.g., depression). Results in changed plasticity, neurophysiological alterations, and changes in neurochemical levels [85.Hermida A.P. et al.Electroconvulsive therapy in depression: current practice and future direction.Psychiatr. Clin. North Am. 2018; 41: 341-353Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar]. genome-wide screening of genetic variants in large populations comparing a control group with a group carrying a specific trait to identify variants significantly associated with the trait [86.Wohland T. Schleinitz D. Identification of disease-related genes using a genome-wide association study approach.in: DiStefano J.K. Disease Gene Identification: Methods and Protocols. Springer, 2018: 113-150Crossref Scopus (1) Google Scholar]. hypothalamic signals communicating with pituitary gland and adrenal glands to regulate glucocorticoid/cortisol levels. Regulates stress response, immune response, and adrenergic and noradrenergic neural circuits [87.Smith S.M. Vale W.W. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress.Dialogues Clin. Neurosci. 2006; 8: 383-395Crossref PubMed Google Scholar]. form of dementia that is associated with deposits of a protein called α-synuclein, or so-called Lewy bodies [88.Outeiro T.F. et al.Dementia with Lewy bodies: an update and outlook.Mol. Neurodegener. 2019; 14: 5Crossref PubMed Scopus (0) Google Scholar]. gene encoding for an intermediate-filament protein. Used to label proliferating neural progenitor cells [80.Gatt A. et al.Expression of neurogenic markers in Alzheimer’s disease: a systematic review and metatranscriptional analysis.Neurobiol. Aging. 2019; 76: 166-180Crossref PubMed Scopus (4) Google Scholar]. neuronal nuclei antigen encoded by RBFOX1 gene. Marker for neuronal differentiation [80.Gatt A. et al.Expression of neurogenic markers in Alzheimer’s disease: a systematic review and metatranscriptional analysis.Neurobiol. Aging. 2019; 76: 166-180Crossref PubMed Scopus (4) Google Scholar]. prediction of risk for a certain disease based on cumulative effects of all known associated genetic variations. The effects of those variations are based on data from genome-wide association studies [92.Cecile A. Janssens J.W. Validity of polygenic risk scores: are we measuring what we think we are?.Hum. Mol. Genet. 2019; 28: R143-R150Crossref PubMed Scopus (0) Google Scholar]. involved in DNA replication and marker for proliferating cells [80.Gatt A. et al.Expression of neurogenic markers in Alzheimer’s disease: a systematic review and metatranscriptional analysis.Neurobiol. Aging. 2019; 76: 166-180Crossref PubMed Scopus (4) Google Scholar]. transcription factor specific to hippocampal GNs in the brain [89.Iwano T. et al.Prox1 postmitotically defines dentate gyrus cells by specifying granule cell identity over CA3 pyramidal cell fate in the hippocampus.Dev. Camb. Engl. 2012; 139: 3051-3062Crossref PubMed Scopus (0) Google Scholar]. marks developing and migrating neurons in the hippocampus [80.Gatt A. et al.Expression of neurogenic markers in Alzheimer’s disease: a systematic review and metatranscriptional analysis.Neurobiol. Aging. 2019; 76: 166-180Crossref PubMed Scopus (4) Google Scholar]. most common form of antidepressant drug (https://www.nhs.uk/conditions/ssri-antidepressants). involved in vascularisation and angiogenesis [90.Karaman S. et al.Vascular endothelial growth factor signaling in development and disease.Development. 2018; 145dev151019Crossref PubMed Scopus (39) Google Scholar].
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