Microglial advances in psychiatric disorders

AI Summary

Microglia are heterogeneous, dynamically adopting phenotypic states to regulate synaptic pruning, neurogenesis and neural circuit function in brain homeostasis.
Chronic pro-inflammatory microglial activation impairs synaptic plasticity, drives neuroinflammation and links to depression, schizophrenia, bipolar disorder and neurodegeneration.
Therapeutic paradigm shift towards precise modulation of microglial functional states, including anti-inflammatory reprogramming, neuromodulation and microglial replacement strategies.

TL;DR (AI Generated)

Dysregulation of microglial activity, particularly chronic pro-inflammatory activation, has been strongly associated with disorders such as major depression, schizophrenia, bipolar disorder, and neurodegenerative diseases, contributing to impaired synaptic plasticity, neuroinflammation, and behavioral dysfunction.

Furthermore, emerging therapeutic strategies targeting microglia were discussed, including anti-inflammatory approaches, functional reprogramming, neuromodulation techniques, and microglial replacement or niche engineering.

Understanding and targeting microglia dynamics may provide innovative and more effective therapeutic pathways for the treatment of psychiatric disorders.

Basic summary

Adv Immunol. 2026;171:371-400. doi: 10.1016/bs.ai.2026.04.007. Epub 2026 May 15.

ABSTRACT

Psychiatric disorders constitute a major global challenge to public health, characterized by complex and multifactorial etiologies involving genetic, environmental, and neurobiological factors. In recent years, growing evidence has highlighted the central role of microglia, the resident immune cells of the central nervous system, in regulating brain homeostasis and in the pathophysiology of neuropsychiatric conditions. Beyond their classic immune functions, microglia actively participate in synaptic pruning, neurogenesis, and the modulation of neural circuits. Dysregulation of microglial activity, particularly chronic pro-inflammatory activation, has been strongly associated with disorders such as major depression, schizophrenia, bipolar disorder, and neurodegenerative diseases, contributing to impaired synaptic plasticity, neuroinflammation, and behavioral dysfunction. This chapter discusses recent advances in microglial biology, emphasizing its functional heterogeneity and dynamic phenotypic states. This chapter explores the main molecular pathways involved in microglia-mediated synaptic remodeling and their implications for the progression of neuropsychiatric disorders. Furthermore, emerging therapeutic strategies targeting microglia were discussed, including anti-inflammatory approaches, functional reprogramming, neuromodulation techniques, and microglial replacement or niche engineering. These advances support a paradigm shift from indiscriminate microglia inhibition to the precise modulation of specific functional states. Understanding and targeting microglia dynamics may provide innovative and more effective therapeutic pathways for the treatment of psychiatric disorders.

PMID:42629132 | DOI:10.1016/bs.ai.2026.04.007

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