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Escartin C, Galea E, Lakatos A, O'Callaghan JP, Petzold GC, Serrano-Pozo A, Steinhäuser C, Volterra A, Carmignoto G, Agarwal A, Allen NJ, Araque A, Barbeito L, Barzilai A, Bergles DE, Bonvento G, Butt AM, Chen WT, Cohen-Salmon M, Cunningham C, Deneen B, De Strooper B, Díaz-Castro B, Farina C, Freeman M, Gallo V, Goldman JE, Goldman SA, Götz M, Gutiérrez A, Haydon PG, Heiland DH, Hol EM, Holt MG, Iino M, Kastanenka KV, Kettenmann H, Khakh BS, Koizumi S, Lee CJ, Liddelow SA, MacVicar BA, Magistretti P, Messing A, Mishra A, Molofsky AV, Murai KK, Norris CM, Okada S, Oliet SH, Oliveira JF, Panatier A, Parpura V, Pekna M, Pekny M, Pellerin L, Perea G, Pérez-Nievas BG, Pfrieger FW, Poskanzer KE, Quintana FJ, Ransohoff RM, Riquelme-Perez M, Robel S, Rose CR, Rothstein JD, Rouach N, Rowitch DH, Semyanov A, Sirko S, Sontheimer H, Swanson RA, Vitorica J, Wanner IB, Wood LB, Wu J, Zheng B, Zimmer ER, Zorec R, Sofroniew MV, Verkhratsky A. Reactive astrocyte nomenclature, definitions, and future directions. Nat Neurosci. 2021 Mar;24(3):312-325. Epub 2021 Feb 15 PubMed.
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UK Dementia Research Institute@UCL and VIB@KuLeuven
These two papers bring the two fields of microglia and of astroglia together, as they reflect a broad discussion among different scientists trying to come to an agreement about the nomenclature in their fields. Clearly, the two papers come to a similar conclusion, i.e., that it is too early to decide yet. Both papers are wake-up calls to leave behind simplistic concepts, such as “activated” or “homeostatic”—especially when using only one experimental approach, for instance transcriptomics, to define cell types.
I believe researchers will adapt how they discuss microglia based on these papers. One of the things we need is more complete integration of different information. A lot of progress is based on simple transcriptomics, but that says little about function or morphology. All the information needs to be integrated when trying to understand the function of a particular cell state.
Following these papers, there will be efforts to classify microglia, and astroglia, and to get insight in the relationship between the different cell types. However, I am not sure that we will really see different microglia. My favorite hypothesis currently is that microglia adapt particular “cell states,” and that those reflect their versatility and their capacity to adapt to the needs of the organism. These are not necessarily different “cell types.” To sort this out, we need to know whether microglia can move from one cell state to another, or whether there are predefined groups of cell types that can expand in function in response to external challenges.
For the time being, I like the advice to provide complete description of the cell state that is investigated, and to be a bit careful with conclusions based on one approach.
View all comments by Bart De StrooperUniversitat Autònoma de Barcelona
I want to elaborate on the suggestion in both articles, on which I am an author, to avoid simplistic binary classifications, such as homeostatic versus activated or neuroprotective versus neurotoxic, when describing the reactions of microglia and astrocytes.
First, it is not only that these cells may adopt numerous states in health and disease, but also that they are highly specialized to act as building blocks in neural circuits, performing many functions that cannot be characterized as "neuroprotection" or "neurotoxicity," as though they were tissue macrophages fighting against infections.
Second, each and every microglial and astrocytic state is arguably the result of a combination of adaptive and maladaptive changes aimed to maintain or restore the roles of these cells and to protect the cells—it is seldom recognized that glia are damaged during diseases, too. If adaptive changes predominate, the states represent resilient phenotypes; since diseases are rare, resilience is probable the prevalent response in a normal life. If, by contrast, maladaptive changes predominate, we should talk about gliopathies and develop therapies aimed to restore original glia functions.
Note that I have managed to talk about glia in CNS diseases without resorting to the term "neuroinflammation." In the astrocyte article, "inflammation" was only used to describe infiltration of immune cells into the brain, whereas in the microglia article, it is explicitly recommended to avoid using "neuroinflammation" as a synonym of microglia responses.
View all comments by Elena GaleaMake a Comment
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