The University of Southampton
University of Southampton Institutional Repository

Dark microglia: a new phenotype predominantly associated with pathological states

Dark microglia: a new phenotype predominantly associated with pathological states
Dark microglia: a new phenotype predominantly associated with pathological states
The past decade has witnessed a revolution in our understanding of microglia. These immune cells were shown to actively remodel neuronal circuits, leading to propose new pathogenic mechanisms. To study microglial implication in the loss of synapses, the best pathological correlate of cognitive decline across chronic stress, aging, and diseases, we recently conducted ultrastructural analyses. Our work uncovered the existence of a new microglial phenotype that is rarely present under steady state conditions, in hippocampus, cerebral cortex, amygdala, and hypothalamus, but becomes abundant during chronic stress, aging, fractalkine signaling deficiency (CX3CR1 knockout mice), and Alzheimer's disease pathology (APP-PS1 mice). Even though these cells display ultrastructural features of microglia, they are strikingly distinct from the other phenotypes described so far at the ultrastructural level. They exhibit several signs of oxidative stress, including a condensed, electron-dense cytoplasm and nucleoplasm making them as “dark” as mitochondria, accompanied by a pronounced remodeling of their nuclear chromatin. Dark microglia appear to be much more active than the normal microglia, reaching for synaptic clefts, while extensively encircling axon terminals and dendritic spines with their highly ramified and thin processes. They stain for the myeloid cell markers IBA1 and GFP (in CX3CR1-GFP mice), and strongly express CD11b and microglia-specific 4D4 in their processes encircling synaptic elements, and TREM2 when they associate with amyloid plaques. Overall, these findings suggest that dark microglia, a new phenotype that we identified based on their unique properties, could play a significant role in the pathological remodeling of neuronal circuits, especially at synapses. GLIA 2016
microglia, synaposes, stress, aging, neurodegenerative diseases
0894-1491
1-14
Bisht, K.
a70290fd-3642-4341-8e4f-a8e5979d119d
Sharma, K.P.
f88cb857-6a16-498c-a357-281ed1de56f3
Lecours, C.
c5dbba75-eaee-47a2-9453-07c2a303b7c9
Sánchez, M.G.
96786834-279e-4ef4-bb88-325f89882cce
El Hajj, H.
691a1c79-3807-43c6-abfc-8ee73d86da60
Milior, G.
59b9bda4-7aac-41bf-800d-374050258e87
Olmos-Alonso, Adrian
c52c3bd9-2cf0-4b55-9214-cb549449db75
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Luheshi, G.
66401a4d-e2dc-4e61-b49d-8e5eb9d68ffe
Vallières, L.
33cf4367-92be-443c-bf98-0c963243232e
Branchi, I.
ecf1c530-7b9b-4715-88eb-7dca80bf9ae3
Maggi, L.
39205efd-b0a6-468c-b04c-fa0a60afe4ec
Limatola, C.
749e9c64-4097-44b2-8827-269141551ef0
Butovsky, O.
7cc4efea-db6e-459f-ac0f-5b9e723a8ec0
Tremblay, M.E.
a65f6e8a-fcfd-4c4f-8f4d-3e65a25beda0
Bisht, K.
a70290fd-3642-4341-8e4f-a8e5979d119d
Sharma, K.P.
f88cb857-6a16-498c-a357-281ed1de56f3
Lecours, C.
c5dbba75-eaee-47a2-9453-07c2a303b7c9
Sánchez, M.G.
96786834-279e-4ef4-bb88-325f89882cce
El Hajj, H.
691a1c79-3807-43c6-abfc-8ee73d86da60
Milior, G.
59b9bda4-7aac-41bf-800d-374050258e87
Olmos-Alonso, Adrian
c52c3bd9-2cf0-4b55-9214-cb549449db75
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Luheshi, G.
66401a4d-e2dc-4e61-b49d-8e5eb9d68ffe
Vallières, L.
33cf4367-92be-443c-bf98-0c963243232e
Branchi, I.
ecf1c530-7b9b-4715-88eb-7dca80bf9ae3
Maggi, L.
39205efd-b0a6-468c-b04c-fa0a60afe4ec
Limatola, C.
749e9c64-4097-44b2-8827-269141551ef0
Butovsky, O.
7cc4efea-db6e-459f-ac0f-5b9e723a8ec0
Tremblay, M.E.
a65f6e8a-fcfd-4c4f-8f4d-3e65a25beda0

Bisht, K., Sharma, K.P., Lecours, C., Sánchez, M.G., El Hajj, H., Milior, G., Olmos-Alonso, Adrian, Gomez-Nicola, Diego, Luheshi, G., Vallières, L., Branchi, I., Maggi, L., Limatola, C., Butovsky, O. and Tremblay, M.E. (2016) Dark microglia: a new phenotype predominantly associated with pathological states. Glia, 1-14. (doi:10.1002/glia.22966). (PMID:26847266)

Record type: Article

Abstract

The past decade has witnessed a revolution in our understanding of microglia. These immune cells were shown to actively remodel neuronal circuits, leading to propose new pathogenic mechanisms. To study microglial implication in the loss of synapses, the best pathological correlate of cognitive decline across chronic stress, aging, and diseases, we recently conducted ultrastructural analyses. Our work uncovered the existence of a new microglial phenotype that is rarely present under steady state conditions, in hippocampus, cerebral cortex, amygdala, and hypothalamus, but becomes abundant during chronic stress, aging, fractalkine signaling deficiency (CX3CR1 knockout mice), and Alzheimer's disease pathology (APP-PS1 mice). Even though these cells display ultrastructural features of microglia, they are strikingly distinct from the other phenotypes described so far at the ultrastructural level. They exhibit several signs of oxidative stress, including a condensed, electron-dense cytoplasm and nucleoplasm making them as “dark” as mitochondria, accompanied by a pronounced remodeling of their nuclear chromatin. Dark microglia appear to be much more active than the normal microglia, reaching for synaptic clefts, while extensively encircling axon terminals and dendritic spines with their highly ramified and thin processes. They stain for the myeloid cell markers IBA1 and GFP (in CX3CR1-GFP mice), and strongly express CD11b and microglia-specific 4D4 in their processes encircling synaptic elements, and TREM2 when they associate with amyloid plaques. Overall, these findings suggest that dark microglia, a new phenotype that we identified based on their unique properties, could play a significant role in the pathological remodeling of neuronal circuits, especially at synapses. GLIA 2016

Text Bisht_et_al-2016-Glia.pdf - Version of Record
Download (1MB)

More information

Accepted/In Press date: 28 December 2015
Published date: 5 February 2016
Keywords: microglia, synaposes, stress, aging, neurodegenerative diseases
Organisations: Biomedicine

Identifiers

Local EPrints ID: 387051
URI: https://eprints.soton.ac.uk/id/eprint/387051
ISSN: 0894-1491
PURE UUID: bf65d3f4-d0c0-4b22-9e51-9e5da91c15fc
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

Catalogue record

Date deposited: 08 Feb 2016 11:32
Last modified: 06 Jun 2018 12:33

Export record

Altmetrics

Contributors

Author: K. Bisht
Author: K.P. Sharma
Author: C. Lecours
Author: M.G. Sánchez
Author: H. El Hajj
Author: G. Milior
Author: Adrian Olmos-Alonso
Author: G. Luheshi
Author: L. Vallières
Author: I. Branchi
Author: L. Maggi
Author: C. Limatola
Author: O. Butovsky
Author: M.E. Tremblay

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×