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

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.

Intrathecal Injection of the Secretome from ALS Motor Neurons Regulated for miR-124 Expression Prevents Disease Outcomes in SOD1-G93A Mice

“…Neuroinflammation is associated with ALS, and glial cell dysregulation is implicated in the initiation/propagation of neurodegeneration [ 49 , 50 ]. Here, based on the promising data obtained for neuronal function with the intrathecal injection of the preconditioned secretome in 12-week-old mSOD1 mice, we wondered whether such beneficial effects could be supported by the prevention of the homeostatic imbalance of microglia and astrocyte activation.…”

“…Microglia activation and astrocyte reactivity contribute to the dissemination of neurodegeneration [ 49 , 50 ]. However, due to the glial cell heterogenous phenotypes, it has been hard to define the roles of microglia and astrocytes in pathological processes.…”

The potential role of HIV-1 latency in promoting neuroinflammation and HIV-1-associated neurocognitive disorder

“…Reactivation of latent HIV-1 causes a microglial shift to a reactive state, resulting in the release of proinflammatory cytokines such as TNF-α, IL-1β, IL-6, IL-8, CCL2, and CCL5, ROS, and RNS [34]. Microglia activation can also cause astrocytes to shift to a reactive state, with secretion of more inflammatory cytokines [72]. Viral proteins such as gp120, Nef, and Tat can directly cause neuronal damage and disrupt astrocyte glutamate transporters, resulting in glutamate imbalance in the brain and excitotoxicity of neurons [18,83].…”

“…Nonetheless, astrocytes probably make important contributions to HAND pathology through indirect mechanisms. Astrocytes become activated during HIV-1 infections, and have disrupted β-catenin signaling, leading to neuronal injury [72]. As seen in the brains of HAND patients and transgenic mice, activated astrocytes can induce migrating monocytes to release inflammatory cytokines that can increase astrocyte-elevated gene-1 expression, leading to glutamate imbalance and neuronal injury [35].…”

Quantification of astrocytic synaptic pruning in hippocampus in response to in vitro Aβ oligomer incubation via colocalization analysis with C1q

“…Astrocytes, which form a bigger subset of glial cells, play a significant role in restructuring of synapses by regular crosstalk with microglia (Chung, Allen and Eroglu, 2015). This crosstalk is mediated by a diverse range of cytokines (Garland, Hartnell and Boche, 2022). C1q of the complement cascade, is one such essential tags which is also referred to as the “eat-me” signal and plays a critical role as a signaling molecule in the pruning of neurons (Iram et al ., 2016) (Kovács et al ., 2021).…”