Microglia and Astrocyte Function and Communication: What Do We Know in Humans?

Emma F Garland,Delphine Boche,Iain J Hartnell

doi:10.3389/fnins.2022.824888

Abstract

Microglia and astrocytes play essential roles in the central nervous system contributing to many functions including homeostasis, immune response, blood–brain barrier maintenance and synaptic support. Evidence has emerged from experimental models of glial communication that microglia and astrocytes influence and coordinate each other and their effects on the brain environment. However, due to the difference in glial cells between humans and rodents, it is essential to confirm the relevance of these findings in human brains. Here, we aim to review the current knowledge on microglia-astrocyte crosstalk in humans, exploring novel methodological techniques used in health and disease conditions. This will include an in-depth look at cell culture and iPSCs, post-mortem studies, imaging and fluid biomarkers, genetics and transcriptomic data. In this review, we will discuss the advantages and limitations of these methods, highlighting the understanding these methods have brought the field on these cells communicative abilities, and the knowledge gaps that remain.

Highlights

Astrocytes and microglia, both types of glial cells, are key cells in the central nervous system (CNS), maintaining homeostasis and supporting the function of neurons (Figure 1)
The importance of microglia/astrocyte crosstalk has recently emerged as an important component of the neurodegenerative aspect of Alzheimer’s disease (AD)
Our current knowledge of microglia/astrocyte communication is based on findings obtained from experimental animal models

Summary

INTRODUCTION

Astrocytes and microglia, both types of glial cells, are key cells in the central nervous system (CNS), maintaining homeostasis and supporting the function of neurons (Figure 1). Microglia are the resident immune cells of the CNS, accounting for 10% of cells (Salter and Stevens, 2017) They are derived from the yolk sac (Ginhoux et al, 2010), and during brain development regulate neurogenesis (Cunningham et al, 2013), promote neuronal survival (Ueno et al, 2013) and participate in synaptic pruning, to ensure appropriate neuronal connections are made and brain maturation occurs (Schafer et al, 2012). Throughout adult life, they continue to interact with their environment, contributing to synaptic communication and ensuring cerebral homeostasis is maintained within the brain by constantly surveying the surrounding parenchyma with their finger-like processes (Boche et al, 2013). Many studies used GFAP to monitor astrocyte proliferation, and it is argued that the increased expression may be related to upregulation in individual cells rather than astrocytic proliferation (Perez-Nievas and Serrano-Pozo, 2018), as observed in a study using the proliferating cell marker PCNA

Method

Findings

CONCLUSION