Abstract
Recent discoveries on the neurobiology of the immunocompetent cells of the central nervous system (CNS), microglia, have been recognized as a growing field of investigation on the interactions between the brain and the immune system. Several environmental contexts such as stress, lesions, infectious diseases, and nutritional and hormonal disorders can interfere with CNS homeostasis, directly impacting microglial physiology. Despite many encouraging discoveries in this field, there are still some controversies that raise issues to be discussed, especially regarding the relationship between the microglial phenotype assumed in distinct contexts and respective consequences in different neurobiological processes, such as disorders of brain development and neuroplasticity. Also, there is an increasing interest in discussing microglial–immune system cross-talk in health and in pathological conditions. In this review, we discuss recent literature concerning microglial function during development and homeostasis. In addition, we explore the contribution of microglia to synaptic disorders mediated by different neuroinflammatory outcomes during pre- and postnatal development, with long-term consequences impacting on the risk and vulnerability to the emergence of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders.
Highlights
Microglia are mononuclear phagocytes known to play an important immunological and homeostatic role in the central nervous system (CNS) [1]
Microglia shift from different stages of activation depends on a cross-talk between neurons, astrocytes, and microglial cells, which is essential for adaptive neuroplasticity
A specific group of CD4+ T cells located in a niche at the choroid plexus acts as “gatekeepers,” mediating local and remote functions within the CNS territory, outside of the brain parenchyma, which is patrolled by microglia [51]
Summary
Microglia are mononuclear phagocytes known to play an important immunological and homeostatic role in the central nervous system (CNS) [1]. Microglia monitor and modulate neuronal circuits [16] and the resulting neuronal activity [17] They control neurogenesis, maintaining the pool of oligodendrocyte progenitor cells (OPC) and normal myelinogenesis [18]. Microglia shift from different stages of activation depends on a cross-talk between neurons, astrocytes, and microglial cells, which is essential for adaptive neuroplasticity. The surveillant microglia are under the control of neuronal factors, such as CD200 and fractalkine (CX3CL1) [22] This interaction is important for microglial colonization to the somatosensory, motor cortex, and hippocampus during early postnatal development, which is impaired in the absence of fractalkine signaling [23]. Hormonal, and inflammatory imbalances, which are already known to impact microglia behavior, and the consequences on the shaping of neural circuitries, as well as the vulnerability to the appearance of neurodevelopmental, neurodegenerative, and neuropsychiatric diseases, such as autistic spectrum disorders and schizophrenia
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