What Do Microglia Really Do in Healthy Adult Brain?

Abstract

Microglia originate from yolk sac-primitive macrophages and auto-proliferate into adulthood without replacement by bone marrow-derived circulating cells. In inflammation, stroke, aging, or infection, microglia have been shown to contribute to brain pathology in both deleterious and beneficial ways, which have been studied extensively. However, less is known about their role in the healthy adult brain. Astrocytes and oligodendrocytes are widely accepted to strongly contribute to the maintenance of brain homeostasis and to modulate neuronal function. On the other hand, contribution of microglia to cognition and behavior is only beginning to be understood. The ability to probe their function has become possible using microglial depletion assays and conditional mutants. Studies have shown that the absence of microglia results in cognitive and learning deficits in rodents during development, but this effect is less pronounced in adults. However, evidence suggests that microglia play a role in cognition and learning in adulthood and, at a cellular level, may modulate adult neurogenesis. This review presents the case for repositioning microglia as key contributors to the maintenance of homeostasis and cognitive processes in the healthy adult brain, in addition to their classical role as sentinels coordinating the neuroinflammatory response to tissue damage and disease.

Antioxidants as a Potential Target against Inflammation and Oxidative Stress in Attention-Deficit/Hyperactivity Disorder

“…Interestingly, serum levels of IL-6 were similar in five-week-old animals of both strains, with elevated levels in 10-week-old SHR, which correlates with that found in children with ADHD [34]. The association between the dysregulation of the inflammatory response and the pathophysiology of ADHD is possible as a result of the role of inflammation in neurogenesis, differentiation, and neuronal function [30,[35][36][37]. Furthermore, neuroinflammation can induce aggravating factors such as blood-brain barrier disruption, altered neurotransmitter metabolism, oxidative stress, and neurodegeneration [38].…”

Microglia and Macrophages in the Pathological Central and Peripheral Nervous Systems

“…During this surveillance, microglia actively engulf synapses and control their number. These actions of microglia, which are termed "synaptic pruning", are said to contribute to the formation of the neural circuits in the developing brain, as well as to homeostasis in the mature brain [4,[6][7][8]. Previously, it was assumed that normal synaptic pruning is the result of competition between the activity levels and activity patterns of nearby neurons; however, it has been demonstrated that synaptic pruning by microglia depends on synaptic activity [9], which allows only active synapses to survive for the normal development of the neural circuits.…”

Microglial contributions to aberrant neurogenesis and pathophysiology of epilepsy

“…By evaluating their surroundings, microglia can actively participate in neurogenesis [ 50 , 51 ] , neurotrophic functions [ 52 ] , neuronal phagocytosis [ 53 ] , modulation of axonal processes [ 54 ] , synapse formation and pruning [ 55 – 57 ] . It has also been proposed that microglia aid in neurotransmitter clearance, specifically glutamate [ 58 ] , due to their upregulation of glutamate transporter GLT-1 in a cortical injury model [ 59 ] . Many of these functions however, are reported to be similarly performed by astrocytes.…”