Differential contribution of microglia and monocytes in neurodegenerative diseases

Baufeld, Caroline; O’Loughlin, Elaine; Calcagno, Narghes; Madore, Charlotte; Butovsky, Oleg

doi:10.1007/s00702-017-1795-7

Cited by 92 publications

(73 citation statements)

References 223 publications

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“…A second approach has been to deplete circulating monocytes with clodronate liposomes, which in some models delays degeneration [13,14], suggesting that infiltrating cells are primarily harmful. However, because the characteristics of both resident and infiltrating cells can change over time, a deeper understanding of their respective roles requires disambiguating their molecular phenotypes and correlating individual phenotypes with cellular behaviors during the onset and progression of neurodegenerative disease ( [15][16][17] for review).…”

Section: Introductionmentioning

confidence: 99%

Monocyte infiltration rather than microglia proliferation dominates the early immune response to rapid photoreceptor degeneration

Karlen

Miller

Wang

et al. 2018

J Neuroinflammation

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Background: Activation of resident microglia accompanies every known form of neurodegeneration, but the involvement of peripheral monocytes that extravasate and rapidly transform into microglia-like macrophages within the central nervous system during degeneration is far less clear. Methods: Using a combination of in vivo ocular imaging, flow cytometry, and immunohistochemistry, we investigated the response of infiltrating cells in a light-inducible mouse model of photoreceptor degeneration. Results: Within 24 h, resident microglia became activated and began migrating to the site of degeneration. Retinal expression of CCL2 increased just prior to a transient period of CCR2 + cell extravasation from the retinal vasculature. Proliferation of microglia and monocytes occurred concurrently; however, there was no indication of proliferation in either population until 72-96 h after neurodegeneration began. Eliminating CCL2-CCR2 signaling blocked monocyte recruitment, but did not alter the extent of retinal degeneration. Conclusions: These results demonstrate that the immune response to photoreceptor degeneration includes both resident microglia and monocytes, even at very early times. Surprisingly, preventing monocyte infiltration did not block neurodegeneration, suggesting that in this model, degeneration is limited by cell clearance from other phagocytes or by the timing of intrinsic cell death programs. These results show monocyte involvement is not limited to disease states that overwhelm or deplete the resident microglial population and that interventions focused on modulating the peripheral immune system are not universally beneficial for staving off degeneration.

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Section: Introductionmentioning

confidence: 99%

Monocyte infiltration rather than microglia proliferation dominates the early immune response to rapid photoreceptor degeneration

Karlen

Miller

Wang

et al. 2018

J Neuroinflammation

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“…CLIC1 protein plays an active role in the transformation of monocytes in resident macrophages. During the neurodegenerative process, systemic monocytes are recruited in the brain [20,24,26,27,32] following chemical messages sent in the blood stream by activated microglia [20][21][22]24,26]. Considering the properties of CLIC1, it is reasonable to think that it is involved in monocyte proliferation, infiltration into the brain parenchyma through the blood brain barrier, acquisition of macrophage characteristics and migration to the infection site.…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that chronic inflammatory states of the CNS, like the neurodegenerative process, activate microglia cells and peripheral blood monocytes. Activated monocytes are recruited in the CNS through the blood brain barrier (BBB) to become tissue-resident macrophages [20][21][22][23][24][25][26]. Our hypothesis is based on the idea that chronically-activated PBMCs, and in particular monocytes, accumulate tmCLIC1 protein.…”

Section: Introductionmentioning

confidence: 99%

CLIC1 Protein Accumulates in Circulating Monocyte Membrane during Neurodegeneration

Carlini

Verduci

Cianci

et al. 2020

IJMS

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Pathologies that lead to neurodegeneration in the central nervous system (CNS) represent a major contemporary medical challenge. Neurodegenerative processes, like those that occur in Alzheimer’s disease (AD) are progressive, and at the moment, they are unstoppable. Not only is an adequate therapy missing but diagnosis is also extremely complicated. The most reliable method is the measurement of beta amyloid and tau peptides concentration in the cerebrospinal fluid (CSF). However, collecting liquid samples from the CNS is an invasive procedure, thus it is not suitable for a large-scale prevention program. Ideally, blood testing is the most manageable and appropriate diagnostic procedure for a massive population screening. Recently, a few candidates, including proteins or microRNAs present in plasma/serum have been identified. The aim of the present work is to propose the chloride intracellular channel 1 (CLIC1) protein as a potential marker of neurodegenerative processes. CLIC1 protein accumulates in peripheral blood mononuclear cells (PBMCs), and increases drastically when the CNS is in a chronic inflammatory state. In AD patients, both immunolocalization and mRNA quantification are able to show the behavior of CLIC1 during a persistent inflammatory state of the CNS. In particular, confocal microscopy analysis and electrophysiological measurements highlight the significant presence of transmembrane CLIC1 (tmCLIC1) in PBMCs from AD patients. Recent investigations suggest that tmCLIC1 has a very specific role. This provides an opportunity to use blood tests and conventional technologies to discriminate between healthy individuals and patients with ongoing neurodegenerative processes.

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“…Microglia activation is implicated in in ammatory responses and depression-like behavior caused by stress [31]. For instance, Elaine al et.…”

Section: Discussionmentioning

confidence: 99%

The monocyte-to-lymphocyte ratio and depression in diabetes patients

Zhou¹,

Wang²,

Li³

2020

Preprint

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Background: The purpose of this study was to determine the association between The monocyte-to-lymphocyte ratio (MLR) and depression with diabetes mellitus.Method: We examined data from the US National Health and Nutrition Examination Survey from 2009 to 2016. Cox proportional hazard models were used to calculate the associations between MLR and depression. For precise investigation of the relationship, we also plotted the smooth curve fit and generated a two-piecewise linear regression model using the penalized spline method.Result: We enrolled 2820 diabetes patients in the database. Diabetes patients who had high MLR tended to be young, female, obese, unmarried, and had low levels of education. For tertile analysis, the ORs and 95% CIs of clinically relevant depression in tertile analysis were 1.03 (0.91, 1.17) for the second group and 1.62 (1.44, 1.82) for the third group in the unadjusted model compared to the control group. A similar trend was observed for the adjusted model and the quartiles analysis. We found the inflection point of MLR was 2.7. There is a positive association between MLR and depression above the threshold, and no relationship was found when MLR was below the threshold in diabetes patients. Conclusion: There is a nonlinear relationship between MLR and depression in diabetes patients. High level of MLR more than the inflection point may add prognostic information for depression in diabetes patients.

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Differential contribution of microglia and monocytes in neurodegenerative diseases

Cited by 92 publications

References 223 publications

Monocyte infiltration rather than microglia proliferation dominates the early immune response to rapid photoreceptor degeneration

Monocyte infiltration rather than microglia proliferation dominates the early immune response to rapid photoreceptor degeneration

CLIC1 Protein Accumulates in Circulating Monocyte Membrane during Neurodegeneration

The monocyte-to-lymphocyte ratio and depression in diabetes patients

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