Cited by 423Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchNeurological Disease Mechanisms and Treatments

The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.

Dark microglia: A new phenotype predominantly associated with pathological states

Open access

Bisht, Kanchan, Sharma, Kaushik P., Lecours, Cynthia, Gabriela Sánchez, Maria, El Hajj, Hassan, Milior, Giampaolo, Olmos‐Alonso, Adrián, Gómez‐Nicola, Diego, Luheshi, Giamal, Vallières, Luc, Branchi, Igor, Maggi, Laura, Limatola, Cristina, Butovsky, Oleg, Tremblay, Marie‐Ève·2016·Glia

DOI 10.1002/glia.22966PMC PMC4949554

Open this paper in CoChat — free account Open PDF

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 (CX 3 CR1 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 CX 3 CR1‐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;64:826–839

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1002/glia.22966

Cites

68 of 68 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

1 retracted

RETRACTED ARTICLE: TGF-β signaling regulates neuronal C1q expression and developmental synaptic refinement
Bialas, A. R., & Stevens, B. (2013) · Nature Neuroscience · doi:10.1038/nn.3560 · Cited by 519
Retracted
The mouse brain in stereotaxic coordinates
Konsman, J. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(03)00088-x · Cited by 16,796
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244
Self-citation
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089
The Classical Complement Cascade Mediates CNS Synapse Elimination
Stevens, B., Allen, N. J., Vazquez, L. E., Howell, G. R., Christopherson, K. S., Nouri, N., Micheva, K. D., Mehalow, A. K., Huberman, A. D., Stafford, B., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.036 · Cited by 3,313
Analysis of Fractalkine Receptor CX3CR1 Function by Targeted Deletion and Green Fluorescent Protein Reporter Gene Insertion
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632
Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor
Parkhurst, C. N., Yang, G., Ninan, I., Savas, J. N., Yates, J. R., Lafaille, J. J., Hempstead, B. L., Littman, D. R., & Gan, W.-B. (2013) · Cell · doi:10.1016/j.cell.2013.11.030 · Cited by 2,599
Immune attack: the role of inflammation in Alzheimer disease
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3880 · Cited by 2,134
From circuits to behaviour in the amygdala
Janak, P. H., & Tye, K. M. (2015) · Nature · doi:10.1038/nature14188 · Cited by 2,011 · cited 1×
“3H).”

Flagged first, then by citations

Show all 68 references

Sorted by citations

Items 301–400 of 423

A unique cell population expressing the Epithelial-Mesenchymal Transition-transcription factor Snail moderates microglial and astrocyte injury responses
Paredes, C. C., Karl, M. T., Popratiloff, A. S., & Miller, R. H. (2023) · PNAS Nexus · doi:10.1093/pnasnexus/pgad334 · Cited by 6
Aging and MPTP Sensitivity Depend on Molecular and Ultrastructural Signatures of Astroglia and Microglia in Mice Substantia Nigra
Abhilash, P. L., Bharti, U., Rashmi, S. K., Philip, M., Raju, T. R., Kutty, B. M., Sagar, B. K. C., & Alladi, P. A. (2025) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-024-01528-8 · Cited by 6
Large-scale effects of prenatal inflammation and early life circadian disruption in mice: Implications for neurodevelopmental disorders
Delorme, T. C., Arcego, D. M., Penichet, D., O’Toole, N., Huebener, N., Silveira, P. P., Srivastava, L. K., & Cermakian, N. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.03.023 · Cited by 7
The Rules of Engagement: Do Microglia Seal the Fate in the Inverse Relation of Glioma and Alzheimer’s Disease?
Cheray, M., Stratoulias, V., Joseph, B., & Grabert, K. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00522 · Cited by 6
Microglia in Cultured Porcine Retina: Qualitative Immunohistochemical Analyses of Reactive Microglia in the Outer Retina
Johansson, K. U. I., & Mohlin, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24010871 · Cited by 6
Morphological analyzes of microglia heterogeneity and dynamics during photoreceptor degeneration in vitro: Presumptive dark microglia in porcine retina
Johansson, K. U. I., Svensson, L. A., & Mohlin, C. (2020) · Experimental Eye Research · doi:10.1016/j.exer.2020.108217 · Cited by 6
Bone marrow-derived myeloid cells transiently colonize the brain during postnatal development and interact with glutamatergic synapses
Carrier, M., Robert, M.-È., St-Pierre, M.-K., Ibáñez, F. G., Gonçalves de Andrade, E., Laroche, A., Picard, K., Vecchiarelli, H. A., Savage, J. C., Boilard, É., et al. (2024) · iScience · doi:10.1016/j.isci.2024.110037 · Cited by 5
Self-citation
Microglia in Human Postmortem Brain Samples: Quantitative Ultrastructural Analysis of Scanning Electron Microscopy Images
St‐Pierre, M., Šimončičová, E., Carrier, M., & Tremblay, M. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2655-9_4 · Cited by 5
Self-citation
Brain remodeling in stroke patients: A comprehensive review of mechanistic and neuroimaging studies
Wang, J., Zhou, J., Zhu, J., Sheng, J., Jiang, R., & Zhang, X. (2025) · Behavioural Brain Research · doi:10.1016/j.bbr.2025.115548 · Cited by 5
Exploring Iron Deposition Patterns Using Light and Electron Microscopy in the Mouse Brain Across Aging and Alzheimer's Disease Pathology Conditions
Lau, V. Z., VanderZwaag, J., Murray, C. J., & Tremblay, M. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70086 · Cited by 6
Self-citation
Evolving insights into the identity and function of dark microglia
Flury, A. G., St‐Pierre, M., Ayata, P., & Tremblay, M. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2025.11.002 · Cited by 7
Self-citation
Implications of Mucin-Type O-Glycosylation in Alzheimer’s Disease
Navarro, N. V., Mundim, G. D. N., & Čudić, M. (2025) · Molecules · doi:10.3390/molecules30091895 · Cited by 5
Microglia and Tanycytes of the Infundibular Recess of the Brain in Early Postnatal Development and during Aging
Суфиева, Д. А., Razenkova, V. A., Antipova, M. V., & Korzhevsky, D. E. (2020) · Russian Journal of Developmental Biology · doi:10.1134/s106236042003008x · Cited by 5
Impact of non-neuronal cells in Alzheimer’s disease from a single-nucleus profiling perspective
Vu, T.-M., Hervé, V., Ulfat, A. K., Lamontagne-Kam, D., & Brouillette, J. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1208122 · Cited by 5
Diving head-first into brain intravital microscopy
Suthya, A. R., Wong, C. H. Y., & Bourne, J. H. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1372996 · Cited by 4
Female mice exhibit similar long-term plasticity and microglial properties between the dorsal and ventral hippocampal poles
Felice, E. D., Bobotis, B. C., Rigillo, G., Khakpour, M., de Andrade, E. G., Benatti, C., Vilella, A., Tascedda, F., Limatola, C., Tremblay, M., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.11.034 · Cited by 5
Self-citation
Ultrastructural disturbances in microglia-neuron interactions in the head of the caudate nucleus in schizophrenia
Uranova, N. A., Vikhreva, O. V., & Рахманова, В. И. (2024) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-024-01956-z · Cited by 5
The Top-Cited Original Articles on the Role of Microglia in Neurodegenerative Diseases: A Bibliometric and Visualized Study
Sun, M., Li, X., Sun, J., Wang, H., Xie, Q., & Wang, M. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.869964 · Cited by 5
Adult IDH Wild-Type Glioblastoma Ultrastructural Investigation Suggests a Possible Correlation between Morphological Biomarkers and Ki-67 Index
Familiari, P., Relucenti, M., Lapolla, P., Palmieri, M., Antonelli, M., Cristiano, L., Barbaranelli, C., Catalano, M., D’Angelo, L., Familiari, G., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11071968 · Cited by 6
Editorial: Hot Topics in Cellular Neuropathology
Hermann, D. M., Popa‐Wagner, A., Peruzzotti‐Jametti, L., & Gunzer, M. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.895861 · Cited by 5
New insights into the role of the endoplasmic reticulum in microglia
Neubrand, V. E., & Sepúlveda, M. R. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.387981 · Cited by 4
Metabolic control of microglia
Garcia-Segura, M. E., Pluchino, S., & Peruzzotti-Jametti, L. (2024) · Advances in Neurobiology · doi:10.1007/978-3-031-55529-9_34 · Cited by 4
Microglia and Sleep Disorders
Picard, K., Dolhan, K., Watters, J. J., & Tremblay, M. (2024) · Advances in neurobiology · doi:10.1007/978-3-031-55529-9_20 · Cited by 4
Self-citation
Impact of prenatal delta-9-tetrahydrocannabinol exposure on mouse brain development: a fetal-to-adulthood magnetic resonance imaging study
Cupo, L., Vecchiarelli, H. A., Gallino, D., VanderZwaag, J., Bradshaw, K., Phan, A., Khakpour, M., Ben‐Azu, B., Guma, E., Fouquet, J. P., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03189-5 · Cited by 5
Self-citation
Assessment of the protective and ameliorative impact of quercetin nanoparticles against neuronal damage induced in the hippocampus by acrolein
Sanad, S. M., Nassar, S. E., & Farouk, R. (2024) · Beni-Suef University Journal of Basic and Applied Sciences · doi:10.1186/s43088-024-00466-0 · Cited by 4
Aging and MPTP-sensitivity depend on molecular and ultrastructural signatures of astroglia and microglia in mice substantia nigraPreprint
Abhilash, P. L., Bharti, U., Rashmi, S. K., Philip, M., Raju, T. R., Kutty, B. M., Sagar, B. K. C., & Alladi, P. A. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.15.422212 · Cited by 4
Ultrastructural characterization of dark microglia during aging in a mouse model of Alzheimer’s disease pathology and in human post-mortem brain samplesPreprint
St‐Pierre, M., Carrier, M., Ibáñez, F. G., Šimončičová, E., Wallman, M., Vallières, L., Parent, M., & Tremblay, M. (2022) · Research Square · doi:10.21203/rs.3.rs-1751270/v1 · Cited by 4
Self-citation
Emerging Techniques for the Study of Microglia: Visualization, Depletion and Fate MappingPreprint
Bobotis, B. C., Halvorson, T., Carrier, M., & Tremblay, M. (2023) · Preprints.org · doi:10.20944/preprints202308.2190.v1 · Cited by 3
Self-citation
Neuroprotective effects of Human Adipose-Derived Stem Cells in AD rat model focusing on CD11b and Synaptophysin
Doshmanziari, M., Sarveazad, A., Moradi, F., Simorgh, S., Shariatpanahi, M., & Eftekharzadeh, M. (2025) · Brain Disorders · doi:10.1016/j.dscb.2025.100285 · Cited by 3
Therapeutic Potentials of the Seaweed-Derived Compounds for Alzheimer’s Disease
Ward, K., Cole, M. H., Griffiths, L. R., Sutherland, H. G. E., Winberg, P. C., Meyer, B. J., & Fernandez, F. (2025) · Molecules · doi:10.3390/molecules30224456 · Cited by 4
Glioinflammation: disease-associated microglia and astrocytes in psychiatric disorders, neurodegeneration, and senescence
Uemura, K., Hiro, S., Attachaipanich, S., Du, R., Yusof, N. I. S. M., Kinoshita, M., Hikosaka, M., & Ohtsuki, G. (2026) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2025.1669272 · Cited by 5
Genetic, Epigenetic, and Transcriptomic Studies of NeuroAIDS
Levine, A. J., Singh, K. K., & Kallianpur, A. R. (2017) · Springer eBooks · doi:10.1007/978-1-4939-7290-6_19 · Cited by 3
The metabolic journey of microglia from early development to adulthood
Das, A., Sadeghdoust, M., Templeman, E. C., & Kaushik, D. K. (2024) · Glial health research. · doi:10.1016/j.ghres.2024.100003 · Cited by 3
How Many Alzheimer–Perusini’s Atypical Forms Do We Still Have to Discover?
Donato, L., Mordà, D., Scimone, C., Alibrandi, S., D’Angelo, R., & Sidoti, A. (2023) · Biomedicines · doi:10.3390/biomedicines11072035 · Cited by 3
Mapping Alzheimer’s Molecular Pathologies in Large-Scale Connectomics Data: A Publicly Accessible Correlative Microscopy ResourcePreprint
Han, X., Li, P. H., Wang, S., Blakely, T. M., Aggarwal, S., Gopalani, B., Sanchez, M., Schalek, R. L., Meirovitch, Y., Lin, Z., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.24.563674 · Cited by 3
Radiation Retinopathy: Microangiopathy-Inflammation-Neurodegeneration
Davids, A., Pompös, I.-M., Kociok, N., Heufelder, J., Skosyrski, S., Reichhart, N., Joussen, A. M., & Wolf, S. A. (2025) · Cells · doi:10.3390/cells14040298 · Cited by 2
Oleanolic Acid and Alzheimer’s Disease: Mechanistic Hypothesis of Therapeutic Potential
Espinosa-Cabello, J. M., Fernández‐Aparicio, Á., González‐Jiménez, E., Perez-Muñoz, G., Castellano, J. M., & Perona, J. S. (2026) · Applied Sciences · doi:10.3390/app16010494 · Cited by 2
Revisiting Functional Heterogeneity of Microglia and Astroglia
Kotova, M. M., Apukhtin, K. V., Nikitin, S. V., & Kalueff, A. V. (2024) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093024060036 · Cited by 2
Cocaine-Induced Microglial Impairment and Its Rehabilitation by PLX-PAD Cell Therapy
Pe’er-Nissan, H., Itzhak, P. S., Gispan, I. H., Ofir, R., & Yadid, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms26010234 · Cited by 2
Dark microglia: a therapeutic target to prevent synaptic loss and neurodegeneration?
Tremblay, M. (2025) · Ageing & Longevity · doi:10.47855/jal9020-2025-1-1 · Cited by 2
Self-citation
Sex differences in microglia as a risk factor for Alzheimer’s disease
Delage, C. I., Rendina, D. N., Malacon, K. E., Tremblay, M., & Bilbo, S. D. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819344-0.00008-9 · Cited by 2
Self-citation
Microglia and Psychiatric Disorders
Couch, A. C. M., & Vernon, A. C. (2021) · Springer eBooks · doi:10.1007/978-3-030-71229-7_8 · Cited by 2
Chronic activation of astrocytic G q GPCR signaling has causal effects on visual LTP formation: implications for neurodegenerative diseasesPreprint
Moukarzel, E., Antoine, S., Guinoiseau, S., Rubino, B., Stinnakre, J., & Agulhon, C. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.16.589763 · Cited by 2
Stressed microglia turn to the dark side in Alzheimer’s disease
Paolo, G. D., & Lewcock, J. W. (2025) · Neuron · doi:10.1016/j.neuron.2025.01.010 · Cited by 1
Spearmint extract Neumentix downregulates amyloid-β accumulation by promoting phagocytosis in APP23 mice
Hu, X., Morihara, R., Fukui, Y., Bian, Y., Sun, H., Ota-Elliott, R. S., Ishiura, H., Abe, K., & Yamashita, T. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149752 · Cited by 1
Unraveling cerebral ultrastructural alterations in TLR4-mediated neuroinflammation via transmission electron microscopy: a systematic preclinical review
da Silva‐Araújo, E. R., Manhães-de-Castro, R., Toscano, A. E., Gouveia, H. J. C. B., de Sá, M. R., Júnior, G. B. A., da Silva, A. N., & Hernández, E. P. (2025) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2025.12.006 · Cited by 1
Microglial response to sleep deprivation depends on the hippocampal region and paradigm used in adult male mice
Kox, J., Picard, K., Šimončičová, E., Vidal, V., Khakpour, M., Wilhelm, S. A., Burns, S. E., Ibáñez, F. G., Ben‐Azu, B., Havekes, R., et al. (2026) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2026.101213 · Cited by 2
Self-citation
Human Microglial Molecular Alterations in Aging and Alzheimer’s Disease
Baldo, K. A. T., Gozlan, E., Chidebe, E. O., Awogbindin, I. O., Prieto, M. O., Dalmacio, L. M. M., Ben-Azu, B., Frenkel, D., & Tremblay, M. (2026) · Cells · doi:10.3390/cells15131159 · Cited by 1
Self-citation
Is amyloid beta peptide a driver of inflammaging?
Kechko, O. I., Moskalev, A. A., Franceschi, C., Mitkevich, V. A., & Makarov, A. А. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103280 · Cited by 1
Environmental and Physiological Cues on the Hypothalamus During Aging
Nehlin, J. O. (2017) · Healthy ageing and longevity · doi:10.1007/978-3-319-63001-4_9 · Cited by 1
Microglia Function in Stroke
Xu, R., Ghori, A., Schneider, U. C., & Vajkoczy, P. (2017) · Translational medicine research · doi:10.1007/978-981-10-5804-2_13 · Cited by 1
Contribution of “Genuine Microglia” to Alzheimer's Disease Pathology
Hashioka, S., Inoue, K., Otsuki, K., Hayashida, M., Wake, R., Kawano, N., Takeshita, H., & Inagaki, M. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.815307 · Cited by 1
New Insights into Microglia as Therapeutic Targets in Alzheimer’s Disease
Mandlik, D. S., Mandlik, S. K., & Choudhary, H. B. (2023) · Current Drug Therapy · doi:10.2174/1574885518666230427100702 · Cited by 2
Quantification of Microglial Engulfment of Synaptic Material Using Flow Cytometry
Ugursu, B., & Wolf, S. A. (2024) · Journal of Visualized Experiments · doi:10.3791/66639 · Cited by 1
Origin, Diversity, and Roles of Microglia
Ris, L. (2024) · Springer eBooks · doi:10.1007/978-3-031-24297-7_9-1 · Cited by 1
Overview of the structure and function of the nervous system
Marinho, L. S. R., Ikebara, J. M., Higa, G. S. V., de Lima-Vasconcellos, T. H., Móvio, M. I., Takada, S. H., & Kihara, A. H. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95730-4.00011-1 · Cited by 2
Introduction to neural engineering
Willerth, S. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95730-4.00019-6 · Cited by 1
Aging and MPTP-Sensitivity Depend on Molecular and Ultrastructural Signatures of Astroglia and Microglia in Mice Substantia NigraPreprint
Abhilash, P. L., Bharti, U., Philip, M., Rashmi, S. K., Raju, T. R., Kutty, B. M., Sagar, B. C., & Alladi, P. A. (2021) · Research Square · doi:10.21203/rs.3.rs-190412/v1 · Cited by 1
Arg1 + microglia are critical for shaping cognition in female micePreprint
Stratoulias, V., Ruiz, R., Kanatani, S., Osman, A. M., Armengol, J. A., Moreno, A. R., Murgoci, A., García-Domínguez, I., Keane, L., Vázquez-Cabrera, G., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.15.456225 · Cited by 1
Self-citation
The Glial Aging & Senescence Hypothesis of Late-onset Alzheimer’sPreprint
Lau, V. Z., Ramer, L. M., & Tremblay, M. (2022) · Preprints.org · doi:10.20944/preprints202109.0437.v2 · Cited by 1
Self-citation
Investigation of microglial diversity in a mouse model of Parkinson’s disease pathologyPreprint
Iovino, L., VanderZwaag, J., Kaur, G., Khakpour, P., Giusti, V., Chiavegato, A., Lopes, L. T., Greggio, E., Tremblay, M., & Civiero, L. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.23.567809 · Cited by 1
Self-citation
Constitutive heterogeneity and response diversity of microglia in pathological conditions
Gertig, U. (2016) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-6043
Microglia phenotypes in aging-associated diseases
Yin, Z. (2017) · University of Groningen research database (University of Groningen / Centre for Information Technology)
Microglial Function in Intracerebral Hemorrhage Injury and Recovery
Cho, A.-H., Michael, N., Cribbs, D. H., & Fisher, M. (2017) · Springer series in translational stroke research · doi:10.1007/978-3-319-66679-2_23
Cell-lineage specificity of primary cilia during epididymis post-natal developmentPreprint
Bernet, A., Bastien, A., Soulet, D., Jerczynski, O., Roy, C., Alves, M. B. R., Lecours, C., Tremblay, M., Bailey, J. L., Robert, C., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/288977
Self-citation
The Impact of Bacteriophage on the Aging Brain and Inflammatory Response: Relevance to Parkinson’s Disease
Beauchamp, S. (2019) · doi:10.22215/etd/2019-13811
Microglia, TREM2, and Therapeutic Methods of Alzheimer’s Disease
Xu, S., Ji, Y., Sha, T., & Li, H. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.100203
How Senescent Glia Drive And Underlie Alzheimer’s Disease: A Predictive ModelPreprint
Lau, V. Z., Ramer, L. M., & Tremblay, M. (2021) · Preprints.org · doi:10.20944/preprints202109.0437.v1
Self-citation
Microglia Aging
Patro, N., Kushwaha, S. S., & Patro, I. K. (2022) · Springer eBooks · doi:10.1007/978-981-16-8313-8_20
An in vitro Study of the Effect of Bacterial Lipopolysaccharide on Transcription Levels of SLC Family Transporter Genes in Microglia
Starovoytova, I. A., & Dominova, I. N. (2022) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093022020193
Principles of gliopathology
Verkhratsky, A., & Butt, A. M. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-821565-4.00005-5
Glial Cells in Alzheimer’s Disease
Verkerke, M. L. (2023) · Utrecht University Repository (Utrecht University) · doi:10.33540/1838
Bone Marrow-Derived Myeloid Cells Colonize the Brain Parenchyma During Postnatal Development and Interact with Synapses in Mice Under Normal Physiological ConditionsPreprint
Carrier, M., Robert, M.-È., St‐Pierre, M., Ibáñez, F. G., de Andrade, E. G., Savage, J. C., Desjardins, M., & Tremblay, M. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4608531
Self-citation
Characterisation of novel immune cell subsets in the central nervous system and its supporting tissues
Etebar, F. (2023) · Queensland University of Technology · doi:10.5204/thesis.eprints.244774
Coptisine Improves Anxiety-Like Behaviors by Regulating the Warburg Effect in Microglia Via Pkm2Preprint
Qi, Y., Zhao, X., Wu, W., Wang, N., Ge, P., Guo, S., Lei, S., Zhou, P., Zhao, L., Tang, Z., et al. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4743962
The contribution of oligodendrocytes to amyloid and tau pathologies in mouse models of Alzheimer’s disease
Sasmita, A. O. (2024) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-10403
JoVE Video Dataset
Ugursu, B., & Wolf, S. A. (2024) · doi:10.3791/66639-v
Qualitative evaluations of reactive microglial heterogeneity in cultured porcine retina.
Johansson, K. U. I., & Mohlin, C. (2024) · PubMed · doi:10.14670/hh-18-772
Origin, Diversity, and Roles of Microglia
Ris, L. (2024) · Springer eBooks · doi:10.1007/978-3-031-60006-7_9
TREM2 expression is differentially associated with microglia and hematogenous monocyte/macrophages proximally and distally located to amyloid plaquesPreprint
Kozyrev, N., Ibáñez, F. G., McKee, C., Traetta, M. E., Tellios, V., Nygard, K. L., Rylett, R. J., Tremblay, M., & Dekaban, G. A. (2025) · Research Square · doi:10.21203/rs.3.rs-6222217/v1
Self-citation
Early micro and nanoscopic responses of microglia to blood-brain barrier modulation by transcranial-focused ultrasoundPreprint
de Andrade, E. G., VanderZwaag, J., Kofoed, R. H., Carrier, M., Picard, K., Pekarik, K. H., Ibáñez, F. G., Khakpour, M., Hynynen, K., Aubert, I., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.17.675183
Self-citation
Additional file 10 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease
Spiteri, A. G., Terry, R. L., Wishart, C. L., Ashhurst, T. M., Campbell, I. L., Hofer, M. J., & King, N. J. C. (2021) · Figshare · doi:10.6084/m9.figshare.15058090
Additional file 12 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease
Spiteri, A. G., Terry, R. L., Wishart, C. L., Ashhurst, T. M., Campbell, I. L., Hofer, M. J., & King, N. J. C. (2021) · Figshare · doi:10.6084/m9.figshare.15058096
Additional file 1 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease
Spiteri, A. G., Terry, R. L., Wishart, C. L., Ashhurst, T. M., Campbell, I. L., Hofer, M. J., & King, N. J. C. (2021) · Figshare · doi:10.6084/m9.figshare.15058099
Additional file 2 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease
Spiteri, A. G., Terry, R. L., Wishart, C. L., Ashhurst, T. M., Campbell, I. L., Hofer, M. J., & King, N. J. C. (2021) · Figshare · doi:10.6084/m9.figshare.15058105
Additional file 5 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease
Spiteri, A. G., Terry, R. L., Wishart, C. L., Ashhurst, T. M., Campbell, I. L., Hofer, M. J., & King, N. J. C. (2021) · Figshare · doi:10.6084/m9.figshare.15058114
Additional file 3 of Translational profiling identifies sex-specific metabolic and epigenetic reprogramming of cortical microglia/macrophages in APPPS1-21 mice with an antibiotic-perturbed-microbiome
Shaik, S. M., Cao, Y., Gogola, J. V., Dodiya, H. B., Zhang, X., Boutej, H., Han, W., Križ, J., & Sisodia, S. S. (2024) · Figshare · doi:10.6084/m9.figshare.26655235
Additional file 4 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease
Spiteri, A. G., Terry, R. L., Wishart, C. L., Ashhurst, T. M., Campbell, I. L., Hofer, M. J., & King, N. J. C. (2021) · Figshare · doi:10.6084/m9.figshare.15058111
Additional file 11 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease
Spiteri, A. G., Terry, R. L., Wishart, C. L., Ashhurst, T. M., Campbell, I. L., Hofer, M. J., & King, N. J. C. (2021) · Figshare · doi:10.6084/m9.figshare.15058093
Additional file 3 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease
Spiteri, A. G., Terry, R. L., Wishart, C. L., Ashhurst, T. M., Campbell, I. L., Hofer, M. J., & King, N. J. C. (2021) · Figshare · doi:10.6084/m9.figshare.15058108
Additional file 9 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease
Spiteri, A. G., Terry, R. L., Wishart, C. L., Ashhurst, T. M., Campbell, I. L., Hofer, M. J., & King, N. J. C. (2021) · Figshare · doi:10.6084/m9.figshare.15058126
Additional file 1 of Translational profiling identifies sex-specific metabolic and epigenetic reprogramming of cortical microglia/macrophages in APPPS1-21 mice with an antibiotic-perturbed-microbiome
Shaik, S. M., Cao, Y., Gogola, J. V., Dodiya, H. B., Zhang, X., Boutej, H., Han, W., Križ, J., & Sisodia, S. S. (2023) · Figshare · doi:10.6084/m9.figshare.24847155
Additional file 2 of Translational profiling identifies sex-specific metabolic and epigenetic reprogramming of cortical microglia/macrophages in APPPS1-21 mice with an antibiotic-perturbed-microbiome
Shaik, S. M., Cao, Y., Gogola, J. V., Dodiya, H. B., Zhang, X., Boutej, H., Han, W., Križ, J., & Sisodia, S. S. (2024) · Figshare · doi:10.6084/m9.figshare.24847215
Additional file 7 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease
Spiteri, A. G., Terry, R. L., Wishart, C. L., Ashhurst, T. M., Campbell, I. L., Hofer, M. J., & King, N. J. C. (2021) · Figshare · doi:10.6084/m9.figshare.15058120
Additional file 8 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease
Spiteri, A. G., Terry, R. L., Wishart, C. L., Ashhurst, T. M., Campbell, I. L., Hofer, M. J., & King, N. J. C. (2021) · Figshare · doi:10.6084/m9.figshare.15058123
Additional file 6 of High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease
Spiteri, A. G., Terry, R. L., Wishart, C. L., Ashhurst, T. M., Campbell, I. L., Hofer, M. J., & King, N. J. C. (2021) · Figshare · doi:10.6084/m9.figshare.15058117
Additional file 1 of Microglia/macrophages are ultrastructurally altered by their proximity to spinal cord injury in adult female mice
St-Pierre, M.-K., Ibáñez, F. G., Kroner, A., & Tremblay, M. (2024) · Figshare · doi:10.6084/m9.figshare.26643385
Self-citation
Additional file 8 of CX3CR1 deficiency aggravates amyloid driven neuronal pathology and cognitive decline in Alzheimer’s disease
Puntambekar, S. S., Moutinho, M., Lin, P. B., Jadhav, V., Tumbleson, D. M., Balaji, A., Benito, M. A., Xu, G., Oblak, A. L., Lasagna‐Reeves, C. A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20175603
Additional file 10 of CX3CR1 deficiency aggravates amyloid driven neuronal pathology and cognitive decline in Alzheimer’s disease
Puntambekar, S. S., Moutinho, M., Lin, P. B., Jadhav, V., Tumbleson, D. M., Balaji, A., Benito, M. A., Xu, G., Oblak, A. L., Lasagna‐Reeves, C. A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20175579
Additional file 9 of CX3CR1 deficiency aggravates amyloid driven neuronal pathology and cognitive decline in Alzheimer’s disease
Puntambekar, S. S., Moutinho, M., Lin, P. B., Jadhav, V., Tumbleson, D. M., Balaji, A., Benito, M. A., Xu, G., Oblak, A. L., Lasagna‐Reeves, C. A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20175606

Authors: Bisht, K., Sharma, K. P., Lecours, C., Gabriela Sánchez, M., El Hajj, H., Milior, G., Olmos‐Alonso, A., Gómez‐Nicola, D., Luheshi, G., Vallières, L., Branchi, I., Maggi, L., Limatola, C., Butovsky, O., & Tremblay, M.
Affiliations: Centre de recherche du CHU de Québec-Université Laval (CA)
Axe Neurosciences Centre De Recherche Du CHU De Québec Québec Québec Canada
Istituto Pasteur (IT)
University of Southampton (GB)
Douglas Mental Health University Institute (CA)
Istituto Superiore di Sanità (IT)
Brigham and Women's Hospital (US)
Corresponding author: Tremblay, Marie‐Ève
ORCID: Bisht, Kanchan
Sharma, Kaushik P.
Milior, Giampaolo
Gómez‐Nicola, Diego
Vallières, Luc
Branchi, Igor
Maggi, Laura
Limatola, Cristina
Butovsky, Oleg
Tremblay, Marie‐Ève
Venue: Glia
Publisher: Wiley
Published: 2016-02-05
Volume: 64
Issue: 5
Pages: 826-839
ISSN: 0894-1491 (ISSN-L)
1098-1136
DOI: 10.1002/glia.22966
PMC: PMC4949554
OpenAlex: W2256955303
Cited by: 421
References: 68
Citations by year: 2026: 25 · 2025: 36 · 2024: 52 · 2023: 48 · 2022: 44 · 2021: 64 · 2020: 42 · 2019: 42 · 2018: 30 · 2017: 26 · 2016: 12
FWCI: 20.09
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Glia (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
ePrints Soton (University of Southampton) (acceptedVersion)
IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders: Natural Sciences and Engineering Research Council of Canada (NSERC) (RGPIN-2014-05308)
Medical Research Council (MR/K022687/1)
The Banting Research Foundation
The Scottish Rite Charitable Foundation of Canada
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: microglial phenotype, oxidative stress, chronic stress, aging, CX3CR1, Alzheimer's disease, APP/PS1 mice, amyloid plaques, TREM2, synaptic loss, dendritic spines, axon terminals, hippocampus, cerebral cortex, amygdala, hypothalamus
MeSH terms: CX3C Chemokine Receptor 1, Formyltetrahydrofolate Dehydrogenase, Aging, Aldehyde Dehydrogenase, Alzheimer Disease, Oxidoreductases Acting on CH-NH Group Donors, Animals, Cerebral Cortex, Disease Models, Animal, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Phenotype, Stress, Psychological, Antigens, CD, Amyloid beta-Protein Precursor, Microglia, Receptors, Chemokine, Green Fluorescent Proteins, Mice, Presenilin-1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Dark microglia: A new phenotype predominantly associated with pathological states

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks