Psychosocial stress on neuroinflammation and cognitive dysfunctions in Alzheimer's disease: the emerging role for microglia?. (June 2017)

• Record Type: Journal Article
• Authors: Piirainen, Sami; Youssef, Andrew; Song, Cai; Kalueff, Allan V.; Landreth, Gary E.; Malm, Tarja; Tian, Li
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 77(2017)
• Page Start: 148
• Page End: 164
• Publication Date: 2017-06
• Subjects: Aβ amyloid-β -- AD Alzheimer's Disease -- AMPA 2-amino-3-(5-methyl-3-hydroxyl-1, 2-oxazol-4-yl) propanoic acid -- APOE apolipoprotein E -- APP amyloid precursor Protein -- ATP adenosine triphosphates -- BBB blood-brain barrier -- BDNF brain-derived neurotrophic factor -- CaMK calcium/calmodulin-dependent protein kinase -- CD cluster of differentiation -- CNS central nervous system -- CR complement receptor -- CX3CR1 CX3C chemokine receptor 1 -- DISC1 disrupted in schizophrenia 1 -- GC glucocorticoid -- GWAS genome-wide association study -- HPA hypothalamic-pituitary-adrenal axis -- IDO indoleamine-2, 3-dioxygenase -- IL Interleukin -- IL-1RA IL-1 receptor antagonist -- LOAD late-onset Alzheimer's Disease -- LPS lipopolysaccharide -- LTP long-term potentiation -- MCI mild cognitive impairment -- NE norepinephrine -- NMDAR N-methyl-D-aspartate receptor -- NSAIDs non-steroidal anti-inflammatory drugs -- PPARγ peroxisome proliferator activated receptor-gamma -- PTSD posttraumatic stress disorder -- TNF-α tumor necrosis factor-α -- TREM2 triggering receptor expressed on myeloid cells 2; Late-onset Alzheimer's disease -- Psychosocial stress -- Microglia -- Amyloid clearance -- Dementia; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2017.01.046
• Languages: English
• ISSNs: 0149-7634

Abstract

Highlights: Psychosocial stress primes microglia that contributes to synaptic dysfunctions. Psychosocial stress exacerbates synaptic dysfunction, cognitive impairment in AD. The detrimental effect may be via stress-induced abnormal microglial functions. Abstract: Chronic psychosocial stress is increasingly recognized as a risk factor for late-onset Alzheimer's disease (LOAD) and associated cognitive deficits. Chronic stress also primes microglia and induces inflammatory responses in the adult brain, thereby compromising synapse-supportive roles of microglia and deteriorating cognitive functions during aging. Substantial evidence demonstrates that failure of microglia to clear abnormally accumulating amyloid-beta (Aβ) peptide contributes to neuroinflammation and neurodegeneration in AD. Moreover, genome-wide association studies have linked variants in several immune genes, such as TREM2 and CD33, the expression of which in the brain is restricted to microglia, with cognitive dysfunctions in LOAD. Thus, inflammation-promoting chronic stress may create a vicious cycle of aggravated microglial dysfunction accompanied by increased Aβ accumulation, collectively exacerbating neurodegeneration. Surprisingly, however, little is known about whether and how chronic stress contributes to microglia-mediated neuroinflammation that may underlie cognitive impairments in AD. This review aims to summarize the currently available clinical and preclinical data and outline potential molecular mechanisms linking stress, microglia and neurodegeneration, to foster future research in this field.