Repression of telomere-associated genes by microglia activation in neuropsychiatric disease

Kronenberg, Golo; Uhlemann, Ria; Schöner, Johanna; Wegner, Stephanie; Boujon, Valérie; Deigendesch, Nikolas; Endres, Matthias; Gertz, Karen

doi:10.1007/s00406-016-0750-1

Cited by 18 publications

(17 citation statements)

References 20 publications

(28 reference statements)

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“…Human microglia are exposed to decades of metabolic stress brought about by a multitude of factors, with continuous cycles of mitosis that promote replicative senescence. In vitro studies have shown that rat and human microglia undergo senescence by progressive telomere shortening [ 31 , 32 ]. Therefore, the deterioration of microglia could be crucial for the development of aging-related neurodegenerative disease.…”

Section: Microglia In the Aged Cnsmentioning

confidence: 99%

Microglia and Aging: The Role of the TREM2–DAP12 and CX3CL1-CX3CR1 Axes

Mecca

Giambanco

Donato

et al. 2018

IJMS

189

138

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Depending on the species, microglial cells represent 5–20% of glial cells in the adult brain. As the innate immune effector of the brain, microglia are involved in several functions: regulation of inflammation, synaptic connectivity, programmed cell death, wiring and circuitry formation, phagocytosis of cell debris, and synaptic pruning and sculpting of postnatal neural circuits. Moreover, microglia contribute to some neurodevelopmental disorders such as Nasu-Hakola disease (NHD), and to aged-associated neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and others. There is evidence that human and rodent microglia may become senescent. This event determines alterations in the microglia activation status, associated with a chronic inflammation phenotype and with the loss of neuroprotective functions that lead to a greater susceptibility to the neurodegenerative diseases of aging. In the central nervous system (CNS), Triggering Receptor Expressed on Myeloid Cells 2-DNAX activation protein 12 (TREM2-DAP12) is a signaling complex expressed exclusively in microglia. As a microglial surface receptor, TREM2 interacts with DAP12 to initiate signal transduction pathways that promote microglial cell activation, phagocytosis, and microglial cell survival. Defective TREM2-DAP12 functions play a central role in the pathogenesis of several diseases. The CX3CL1 (fractalkine)-CX3CR1 signaling represents the most important communication channel between neurons and microglia. The expression of CX3CL1 in neurons and of its receptor CX3CR1 in microglia determines a specific interaction, playing fundamental roles in the regulation of the maturation and function of these cells. Here, we review the role of the TREM2-DAP12 and CX3CL1-CX3CR1 axes in aged microglia and the involvement of these pathways in physiological CNS aging and in age-associated neurodegenerative diseases.

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Section: Microglia In the Aged Cnsmentioning

confidence: 99%

Microglia and Aging: The Role of the TREM2–DAP12 and CX3CL1-CX3CR1 Axes

Mecca

Giambanco

Donato

et al. 2018

IJMS

189

138

View full text Add to dashboard Cite

show abstract

“…Post-mortem research shows a significant reduction in telomere length across brain regions, especially in the hippocampus, of patients with MDD (Mamdani et al, 2016 ). Repression of telomere-associated genes leads to microglial senescence, a mechanism of neuropsychiatric diseases (Kronenberg et al, 2017 ).…”

Section: Telomerase and Diseases In The Central Nervous Systemmentioning

confidence: 99%

The Emerging Roles for Telomerase in the Central Nervous System

Liu

Nemes

Zhou

2018

Front. Mol. Neurosci.

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Telomerase, a specialized ribonucleoprotein enzyme complex, maintains telomere length at the 3′ end of chromosomes, and functions importantly in stem cells, cancer and aging. Telomerase exists in neural stem cells (NSCs) and neural progenitor cells (NPCs), at a high level in the developing and adult brains of humans and rodents. Increasing studies have demonstrated that telomerase in NSCs/NPCs plays important roles in cell proliferation, neuronal differentiation, neuronal survival and neuritogenesis. In addition, recent works have shown that telomerase reverse transcriptase (TERT) can protect newborn neurons from apoptosis and excitotoxicity. However, to date, the link between telomerase and diseases in the central nervous system (CNS) is not well reviewed. Here, we analyze the evidence and summarize the important roles of telomerase in the CNS. Understanding the roles of telomerase in the nervous system is not only important to gain further insight into the process of the neural cell life cycle but would also provide novel therapeutic applications in CNS diseases such as neurodegenerative condition, mood disorders, aging and other ailments.

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“…Magnetic-activated cell separation (MACS) has been used to isolate microglia and monocyte-derived macrophages (MMϕ) in mouse models of Alzheimer’s disease (Kronenberg et al, 2017), glioma (Szulzewsky et al, 2015), ischemic stroke (Yang B. et al, 2016), and ICH (Lan et al, 2017a). However, to our knowledge, no protocol exists for separating the two cell types after ICH.…”

Section: Introductionmentioning

confidence: 99%

Expression of Tmem119/Sall1 and Ccr2/CD69 in FACS-Sorted Microglia- and Monocyte/Macrophage-Enriched Cell Populations After Intracerebral Hemorrhage

Lan

Han

et al. 2019

Front. Cell. Neurosci.

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Activation and polarization of microglia and macrophages are critical events in neuroinflammation and hematoma resolution after intracerebral hemorrhage (ICH). However, distinguishing microglia and monocyte-derived macrophages histologically can be difficult. Although they share most cell surface markers, evidence indicates that the gene regulation and function of these two cell types might be different. Flow cytometry is the gold standard for discriminating between the two cell populations, but it is rarely used in the ICH research field. We developed a flow cytometry protocol to identify and sort microglia and monocyte-derived macrophages from mice that have undergone well-established ICH models induced by collagenase or blood injection. In addition, we combined a recently established magnetic-activated cell separation system that allows eight tissue samples to be assessed together. This protocol can be completed within 5–8 h. Sorted cells are fully preserved and maintain expression of microglia-specific (Tmem119/Sall1) and macrophage-specific (Ccr2/CD69) markers. They retain phagocytic ability, respond to lipopolysaccharide stimulation, and engulf fluorescent latex beads. Thus, this protocol represents a very important tool for researching microglial and monocyte-derived macrophage biologic function after ICH and other brain diseases.

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Repression of telomere-associated genes by microglia activation in neuropsychiatric disease

Cited by 18 publications

References 20 publications

Microglia and Aging: The Role of the TREM2–DAP12 and CX3CL1-CX3CR1 Axes

Microglia and Aging: The Role of the TREM2–DAP12 and CX3CL1-CX3CR1 Axes

The Emerging Roles for Telomerase in the Central Nervous System

Expression of Tmem119/Sall1 and Ccr2/CD69 in FACS-Sorted Microglia- and Monocyte/Macrophage-Enriched Cell Populations After Intracerebral Hemorrhage

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