Should We Stop Saying 'Glia' and 'Neuroinflammation'?. Issue 6 (June 2017)

• Record Type: Journal Article
• Authors: Masgrau, Roser; Guaza, Carmen; Ransohoff, Richard M.; Galea, Elena
• Is Part Of: Trends in molecular medicine. Volume 23:Issue 6(2017)
• Page Start: 486
• Page End: 500
• Publication Date: 2017-06
• Subjects: cell replacement -- central nervous system circuits -- central nervous system repair -- computation -- induced pluripotent stem cell -- single-cell RNA sequencing; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; Physiology, Pathological -- Periodicals; 572.8
• DOI: 10.1016/j.molmed.2017.04.005
• Languages: English
• ISSNs: 1471-4914

Abstract

Abstract : Central nervous system (CNS) therapeutics based on the theoretical framework of neuroinflammation have only barely succeeded. We argue that a problem may be the wrong use of the term 'neuroinflammation' as a distinct nosological entity when, based on recent evidence, it may not explain CNS disease pathology. Indeed, the terms 'neuroinflammation' and 'glia' could be obsolete. First, unbiased molecular profiling of CNS cell populations and individual cells reveals striking phenotypic heterogeneity in health and disease. Second, astrocytes, microglia, oligodendrocytes, and NG2 cells may contribute to higher-brain functions by performing actions beyond housekeeping. We propose that CNS diseases be viewed as failed circuits caused in part by disease-specific dysfunction of cells traditionally called 'glia', and hence, favor therapies promoting their functional recovery. Trends: Single-cell imaging and multicellular recordings suggest advanced information integration (i.e., 'computation') in astrocytes, microglia, oligodendrocytes, and NG2 cells beyond housekeeping. Molecular profiling of cell populations and single cells challenges traditional functional classifications and reveals heterogeneous reactions in disease, resulting in many possible cell combinations and multiple circuits. This makes it necessary to employ systems biology to explore the CNS. CNS diseases are circuit diseases caused by astrocyte, microglia, oligodendrocyte, or NG2-cell failures, as much as by neuronal damage. Hence, the need for therapies that restore the function of non-neuronal cells should be considered. Cells and organoids derived from induced pluripotent stem cells are necessary models of human disease, particularly due to the failure of clinical trials based solely on animal data. To advance knowledge, lexicon in neuroscience must swiftly adapt to new discoveries.