7. The role of microglia in stress-induced depression

Kreisel, Tirzah; Frank, Marion E.; Licht, Tamar; Reshef, R.; Ben-Menachem-Zidon, O; Baratta, Michael V.; Maier, Steven F.; Raz, Yael

doi:10.1016/j.bbi.2014.06.027

Cited by 7 publications

(8 citation statements)

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“…With the pro-inflammatory shift of the aging CNS, there is proliferation of both activated microglia and astrocytes resulting in continuous production of pro-inflammatory cytokines 33 . This process is further amplified in depression and Alzheimer’s disease, whereby chronic stress 34 and amyloid beta (Aβ) 35 respectively disrupts the microglia activity, leading to further release of the pro-inflammatory cytokines, interleukins and chemokines. In addition, depression and Alzheimer’s disease cause alteration in the BBB, allowing permeability of the peripheral inflammatory cells into the CNS 36 , further enhancing a state of neuro-inflammation with consequent tissue damage.…”

Section: Introductionmentioning

confidence: 99%

IL-1β, IL-6, TNF- α and CRP in Elderly Patients with Depression or Alzheimer’s disease: Systematic Review and Meta-Analysis

Tam

Zhang

et al. 2018

Sci Rep

399

218

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We carried out systematic review and meta-analysis to evaluate whether peripheral levels of pro-inflammatory markers including Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF- α) and C-Reactive Protein (CRP) are significantly higher in elderly with depression and Alzheimer’s disease. We searched Pubmed, PsycINFO and Embase, and thirty-four relevant studies (2609 with Depression, 1645 with Alzheimer’s disease and 14363 Controls) were included. Compared with controls, IL-1β (pooled standardized mean difference [SMD]: 0.642; 95% confidence interval [CI]: 0.078–1.206; significant heterogeneity: I2 = 86.28%) and IL-6 (pooled SMD: 0.377; 95% CI: 0.156–0.598; significant heterogeneity: I2 = 88.75%) were significantly elevated in depression. There was no difference in TNF-α (p = 0.351) and CRP (p = 0.05) between those with depression and controls. Compared with controls, IL-1β (pooled SMD: 1.37, 95% CI: 0.06–2.68, significant heterogeneity: I2 = 96.01%) was significantly elevated in Alzheimer’s disease. There were no differences in IL-6 (p = 0.138), TNF-α (p = 0.451) and CRP (p = 0.07) between elderly with Alzheimer’s disease and controls. After Bonferroni adjustment, only IL-6 remained significantly higher in depression. Elderly with depression have higher IL-6 than controls, while those with Alzheimer’s disease did not have higher peripheral inflammatory markers.

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Section: Introductionmentioning

confidence: 99%

IL-1β, IL-6, TNF- α and CRP in Elderly Patients with Depression or Alzheimer’s disease: Systematic Review and Meta-Analysis

Tam

Zhang

et al. 2018

Sci Rep

399

218

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“…However, on a mere environmental level, psychosocial stress is still the most common and major risk factor of depression [14,[19][20][21][22][23][24][25]. Concerning the neurobiological link between stress and depression, several studies have highlighted the role of microglia and macrophage (M/ Ms) activation [18,[26][27][28][29][30][31][32] mediated by purinergic signalling via the membrane-bound adenosine triphosphate (ATP) receptor P2X7 (P2X7R) [33][34][35][36][37][38][39][40]. On a genetic level, studies in humans and mice have found an association between polymorphisms in the P2RX7 gene and depressive symptoms [41][42][43][44][45][46].…”

Section: Introductionmentioning

confidence: 99%

P2X7R antagonists in chronic stress-based depression models: a review

Muecke-Heim

Ries

Urbina

et al. 2021

Eur Arch Psychiatry Clin Neurosci

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Depression affects around 320 million people worldwide. Growing evidence proposes the immune system to be the core interface between psychosocial stress and the neurobiological and behavioural features of depression. Many studies have identified purinergic signalling via the P2X7 receptor (P2X7R) to be of great importance in depression genesis yet only a few have evaluated P2X7R antagonists in chronic stress-based depression models. This review summarizes their findings and analyses their methodology. The four available studies used three to nine weeks of unpredictable, chronic mild stress or unpredictable, chronic stress in male mice or rats. Stress paradigm composition varied moderately, with stimuli being primarily psychophysical rather than psychosocial. Behavioural testing was performed during or after the last week of stress application and resulted in depressive-like behaviours, immune changes (NLRP3 assembly, interleukin-1β level increase, microglia activation) and neuroplasticity impairment. During the second half of each stress paradigm, a P2X7R antagonist (Brilliant Blue G, A-438079, A-804598) was applied. Studies differed with regard to antagonist dosage and application timing. Nonetheless, all treatments attenuated the stress-induced neurobiological changes and depressive-like behaviours. The evidence at hand underpins the importance of P2X7R signalling in chronic stress and depression. However, improvements in study planning and reporting are necessary to minimize experimental bias and increase data purview. To achieve this, we propose adherence to the Research Domain Criteria and the STRANGE framework.

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“…Studies have shown that these cells are responsible for inflammatory and degenerative changes in the brain during aging (Schipper, 1996 ; Conde and Streit, 2006 ), psychological stress (Avitsur et al, 2005 ), ischemia (Nedergaard and Dirnagl, 2005 ; Shichita et al, 2012 ), and in the presence of harmful metabolites such as amyloid-β and tau peptides (Nagele et al, 2004 ). These cells also play a significant role in disruption of neuroplasticity and exacerbation of depression during psychological stress (Kreisel et al, 2014b ).…”

Section: Introductionmentioning

confidence: 99%

Microglia: An Interface between the Loss of Neuroplasticity and Depression

Singhal

Baune

2017

Front. Cell. Neurosci.

171

103

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Depression has been widely accepted as a major psychiatric disease affecting nearly 350 million people worldwide. Research focus is now shifting from studying the extrinsic and social factors of depression to the underlying molecular causes. Microglial activity is shown to be associated with pathological conditions, such as psychological stress, pathological aging, and chronic infections. These are primary immune effector cells in the CNS and regulate the extensive dialogue between the nervous and the immune systems in response to different immunological, physiological, and psychological stressors. Studies have suggested that during stress and pathologies, microglia play a significant role in the disruption of neuroplasticity and have detrimental effects on neuroprotection causing neuroinflammation and exacerbation of depression. After a systematic search of literature databases, relevant articles on the microglial regulation of bidirectional neuroimmune pathways affecting neuroplasticity and leading to depression were reviewed. Although, several hypotheses have been proposed for the microglial role in the onset of depression, it is clear that all molecular pathways to depression are linked through microglia-associated neuroinflammation and hippocampal degeneration. Molecular factors such as an excess of glucocorticoids and changes in gene expression of neurotrophic factors, as well as neuro active substances secreted by gut microbiota have also been shown to affect microglial morphology and phenotype resulting in depression. This review aims to critically analyze the various molecular pathways associated with the microglial role in depression.

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7. The role of microglia in stress-induced depression

Cited by 7 publications

References 0 publications

IL-1β, IL-6, TNF- α and CRP in Elderly Patients with Depression or Alzheimer’s disease: Systematic Review and Meta-Analysis

IL-1β, IL-6, TNF- α and CRP in Elderly Patients with Depression or Alzheimer’s disease: Systematic Review and Meta-Analysis

P2X7R antagonists in chronic stress-based depression models: a review

Microglia: An Interface between the Loss of Neuroplasticity and Depression

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