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Cited by 229

The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

Activation of microglial N‐methyl‐D‐aspartate receptors triggers inflammation and neuronal cell death in the developing and mature brain

Kaindl, Angela M., Degos, Vincent, Peineau, Stéphane, Gouadon, Elodie, Chhor, Vibol, Loron, Gauthier, Le Charpentier, Tifenn, Josserand, Julien, Ali, Carine, Vivien, Denis, Collingridge, Graham L., Lombet, Alain, Issa, Lina, Rene, Frédérique, Loeffler, Jean‐Philippe, Kavelaars, Annemieke, Verney, Catherine, Mantz, Jean, Gressens, Pierre·2012·Annals of Neurology
DOI 10.1002/ana.23626
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Abstract

Objective: Activated microglia play a central role in the inflammatory and excitotoxic component of various acute and chronic neurological disorders. However, the mechanisms leading to their activation in the latter context are poorly understood, particularly the involvement of N‐methyl‐D‐aspartate receptors (NMDARs), which are critical for excitotoxicity in neurons. We hypothesized that microglia express functional NMDARs and that their activation would trigger neuronal cell death in the brain by modulating inflammation. Methods and Results: We demonstrate that microglia express NMDARs in the murine and human central nervous system and that these receptors are functional in vitro. We show that NMDAR stimulation triggers microglia activation in vitro and secretion of factors that induce cell death of cortical neurons. These damaged neurons are further shown to activate microglial NMDARs and trigger a release of neurotoxic factors from microglia in vitro, indicating that microglia can signal back to neurons and possibly induce, aggravate, and/or maintain neurologic disease. Neuronal cell death was significantly reduced through pharmacological inhibition or genetically induced loss of function of the microglial NMDARs. We generated Nr1 LoxP+/+LysM Cre+/− mice lacking the NMDAR subunit NR1 in cells of the myeloid lineage. In this model, we further demonstrate that a loss of function of the essential NMDAR subunit NR1 protects from excitotoxic neuronal cell death in vivo and from traumatic brain injury. Interpretation: Our findings link inflammation and excitotoxicity in a potential vicious circle and indicate that an activation of the microglial NMDARs plays a pivotal role in neuronal cell death in the perinatal and adult brain. ANN NEUROL 2012;72:536–549

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Metadata

Authors
Kaindl, A. M., Degos, V., Peineau, S., Gouadon, E., Chhor, V., Loron, G., Le Charpentier, T., Josserand, J., Ali, C., Vivien, D., Collingridge, G. L., Lombet, A., Issa, L., Rene, F., Loeffler, J., Kavelaars, A., Verney, C., Mantz, J., & Gressens, P.
Venue
Annals of Neurology
Publisher
Wiley
Published
2012-10
Volume
72
Issue
4
Pages
536-549
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
DOI
10.1002/ana.23626
OpenAlex
W2034101077
Cited by
229
References
10
FWCI
7.74
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Activation of microglial N‐methyl‐D‐aspartate receptors triggers inflammation and neuronal cell death in the developing and mature brain. https://app.cochat.ai/papers/10.1002/ana.23626
The paper
Kaindl, A. M., Degos, V., Peineau, S., Gouadon, E., Chhor, V., Loron, G., Le Charpentier, T., Josserand, J., Ali, C., Vivien, D., Collingridge, G. L., Lombet, A., Issa, L., Rene, F., Loeffler, J., Kavelaars, A., Verney, C., Mantz, J., & Gressens, P. (2012). Activation of microglial N‐methyl‐D‐aspartate receptors triggers inflammation and neuronal cell death in the developing and mature brain. Annals of Neurology. https://doi.org/10.1002/ana.23626

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.