Plasticity of microglia

Abstract

Microglial cells are the scions of foetal macrophages which invade the neural tube early during embryogenesis. The nervous tissue environment instigates the phenotypic metamorphosis of foetal macrophages into idiosyncratic surveilling microglia, which are generally characterised by a small cell body and highly ramified motile processes that constantly scan the nervous tissue for signs of changes in homeostasis and allow microglia to perform crucial homeostatic functions. The surveilling microglial phenotype is evolutionarily conserved from early invertebrates to humans. Despite this evolutionary conservation, microglia show substantial heterogeneity in their gene and protein expression, as well as morphological appearance. These differences are age, region and context specific and reflect a high degree of plasticity underlying the life‐long adaptation of microglia, supporting the exceptional adaptive capacity of the central nervous system. Microgliocytes are essential elements of cellular network formation and refinement in the developing nervous tissue. Several distinct patrolling modes of microglial processes contribute to the formation, modification, and pruning of synapses; to the support and protection of neurones through microglial–somatic junctions; and to the control of neuronal and axonal excitability by specific microglia–axonal contacts. In pathology, microglia undergo proliferation and reactive remodelling known as microgliosis, which is context dependent, yet represents an evolutionarily conserved defence response. Microgliosis results in the emergence of multiple disease and context‐specific reactive states; in addition, neuropathology is associated with the appearance of specific protective or recovery microglial forms. In summary, the plasticity of microglia supports the development and functional activity of healthy nervous tissue and provides highly sophisticated defences against disease.

Microglial Inflammatory-Metabolic Pathways and Their Potential Therapeutic Implication in Major Depressive Disorder

“…However, at both transcriptional and functional levels, microglia appear to be more complex and dynamic than anticipated. This might explain why engagement of microglia can be either neuroprotective or neurotoxic, leading to attenuation or exacerbation of disease progression ( 10 , 15 , 136 ) depending on the context. According to the traditional classification of macrophages/microglia, during microglial activation following an inflammatory insult, cell morphology is altered either to M1, the typically activated phenotype, or to M2, an alternative activated phenotype; and this phenotypic switch depends on the type of insult.…”

“…It has been shown that INF is a canonical cytokine that can polarize microglia toward M1. It is noteworthy that the classification of the M1 and M2 phenotypes have been challenged ( 10 , 136 , 137 ). The reason is that such classification has been defined mainly based on in vitro studies of peripheral macrophages and that M1 and M2 states fail to emerge in brain resident microglia.…”

Adamantinomatous craniopharyngioma cyst fluid can trigger inflammatory activation of microglia to damage the hypothalamic neurons by inducing the production of β-amyloid

“…2 B). Through the expression of known markers expressed by some specific hypothalamic cell clusters [ 42 – 46 ], we determined the cell type represented by each cluster; that is, clusters 0, 1, 3, 5, 8, and 9 were neurons (snap25+/syt1+), clusters 7, 11, and 15 were microglia (csf1r+/cx3cr1+), clusters 4 and 13 were astrocytes (agt+), clusters 2 and 10 were oligodendrocyte glial cells (cldn11+), cluster 6 was oligodendrocyte precursor cells (pdgfra+/olig1+), cluster 12 was tanycytes (rax+/crym+), cluster 16 was dural cells (mgp+), and cluster 14 was pia mater cells (lum+) (Fig. 2 C).…”

“…After removing the mitochondrial genes from all the cells through an unsupervised strategy, clustering was performed, and 16 populations were found. Through the expression of markers expressed by some specific cell clusters [ 42 – 46 ], we determined the cell type represented by each cluster and identified a large number of glial cells, including microglia (Additional file 4 : Fig. S4C).…”

Neurodevelopment in Children Exposed to Zika in utero: Clinical and Molecular Aspects

“…Glial cells can also participate in neuronal migration, potentially contributing to the development of CZS. Although microglial cells can adopt the inflammatory phenotype to exert neuroprotective functions ( Augusto-Oliveira et al, 2021 ), their persistent activation can be associated with chronic neuroinflammation. This potential event can link Zika infection both to microcephaly and to neurodegenerative/neuropsychiatric diseases in adults ( Beys-da-Silva et al, 2020 ).…”