Roles of Microglia in Synaptogenesis, Synaptic Pruning, and Synaptic Plasticity in Physiological Conditions and Central Nervous System Disorders
Open accessAbstract
Microglia are resident immune cells in the brain that have been widely studied for their immune surveillance and phagocytosis. In recent years, the important role of microglia in synapse formation, elimination, and plasticity is gradually being recognized. Synapses are the main communication mode between neurons. They undergo constant changes in quantity and plasticity throughout the life cycle, which is the basis of learning and memory. Microglia are highly motile, branched forms that monitor the microenvironment of the central nervous system (CNS) and promote synapse formation and maturation. They recognize and phagocytose redundant synapses through specific phagocytosis receptors. Furthermore, microglia regulate synaptic plasticity by releasing various effectors. The roles of microglia on synapses ensure the proper function of neural networks. Synaptic dysfunction and microglia activation are common features in CNS disorders, such as Alzheimer's disease, Parkinson's disease, ischemic stroke, cerebral hemorrhage, traumatic brain injury, multiple sclerosis, and epilepsy. Highly heterogeneous microglia exhibit diverse functions in these diseases and participate in disease progression by exacerbating or inhibiting synaptic dysfunction, in addition to neuroimmune and inflammation. In this article, we summarize the role of microglia on synapses under physiological conditions and in CNS disorders. We highlight the possible mechanisms by which microglia regulate synapse function in CNS disorders and how this affects the progression of the diseases. We aim to explore potential therapeutic targets for CNS disorders.
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In homeostasis, microglia continuously survey the parenchyma, support neuronal integrity, contribute to synaptic remodeling, release trophic factors, and clear debris.
“Even in homeostasis, microglia continuously survey the parenchyma [6], support neuronal integrity [7], contribute to synaptic remodeling [8], release trophic factors [8], and clear debris [9]”
From Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis? (2026) · cites this paper as [8]
The older binary language of resting versus activated microglia is too limited.
“This older binary language is now considered too limited.”
From Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis? (2026) · cites this paper as [8]
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- Authors
- Xie, M., Wang, T., Feng, J., Ma, D., Feng, L., & Hao, Y.
- Affiliations
- Utrecht University (NL)
- Jilin University (CN)
- First Hospital of Jilin University (CN)
- Corresponding author
- Feng, Liangshu
- Hao, Yulei
- Venue
- Current Neuropharmacology
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2025-02-26
- Volume
- 23
- Issue
- 1
- Pages
- 2-35
- ISSN
- 1570-159X (ISSN-L)
- PMC
- PMC13054735
- OpenAlex
- W4408003570
- Cited by
- 7
- References
- 0
- Citations by year
- 2026: 5 · 2025: 2
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- Licence
- cc-by
- Locations
- Current Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- microglia, synaptogenesis, synaptic pruning, synaptic plasticity, microglial phagocytosis, microglial heterogeneity, neuroinflammation, neuroimmune regulation, Alzheimer's disease, Parkinson's disease, ischemic stroke, cerebral hemorrhage, traumatic brain injury, multiple sclerosis, epilepsy, synaptic dysfunction, therapeutic target
- MeSH terms
- Animals, Central Nervous System Diseases, Humans, Neuronal Plasticity, Synapses, Microglia, Neurogenesis
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