Cytokine Signalling at the Microglial Penta-Partite Synapse
Overview
Chemistry
Molecular Biology
Affiliations
Microglial cell processes form part of a subset of synaptic contacts that have been dubbed microglial tetra-partite or quad-partite synapses. Since tetrapartite may also refer to the presence of extracellular matrix components, we propose the more precise term microglial penta-partite synapse for synapses that show a microglial cell process in close physical proximity to neuronal and astrocytic synaptic constituents. Microglial cells are now recognised as key players in central nervous system (CNS) synaptic changes. When synaptic plasticity involving microglial penta-partite synapses occurs, microglia may utilise their cytokine arsenal to facilitate the generation of new synapses, eliminate those that are not needed anymore, or modify the molecular and structural properties of the remaining synaptic contacts. In addition, microglia-synapse contacts may develop de novo under pathological conditions. Microglial penta-partite synapses have received comparatively little attention as unique sites in the CNS where microglial cells, cytokines and other factors they release have a direct influence on the connections between neurons and their function. It concerns our understanding of the penta-partite synapse where the confusion created by the term "neuroinflammation" is most counterproductive. The mere presence of activated microglia or the release of their cytokines may occur independent of inflammation, and penta-partite synapses are not usually active in a neuroimmunological sense. Clarification of these details is the main purpose of this review, specifically highlighting the relationship between microglia, synapses, and the cytokines that can be released by microglial cells in health and disease.
The Role of Glial Cells in the Pathophysiology of Epilepsy.
Onat F, Andersson M, Carcak N Cells. 2025; 14(2).
PMID: 39851521 PMC: 11763453. DOI: 10.3390/cells14020094.
Toledano A, Rodriguez-Casado A, Alvarez M, Toledano-Diaz A Brain Sci. 2024; 14(11).
PMID: 39595866 PMC: 11591712. DOI: 10.3390/brainsci14111101.
Nicotine is an Immunosuppressant: Implications for Women's Health and Disease.
White A, Craig A, Richie D, Corley C, Sadek S, Barton H J Neuroimmunol. 2024; 397:578468.
PMID: 39461120 PMC: 11653054. DOI: 10.1016/j.jneuroim.2024.578468.
Bioelectronic Medicine: a multidisciplinary roadmap from biophysics to precision therapies.
Gonzalez-Gonzalez M, Conde S, Latorre R, Thebault S, Pratelli M, Spitzer N Front Integr Neurosci. 2024; 18:1321872.
PMID: 38440417 PMC: 10911101. DOI: 10.3389/fnint.2024.1321872.
Major depressive disorder: hypothesis, mechanism, prevention and treatment.
Cui L, Li S, Wang S, Wu X, Liu Y, Yu W Signal Transduct Target Ther. 2024; 9(1):30.
PMID: 38331979 PMC: 10853571. DOI: 10.1038/s41392-024-01738-y.