Abstract
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.
Highlights
Brain and Mind Centre, Faculty of Medicine and Health, The University of Sydney, Faculty of Medicine, Health & Human Sciences, Macquarie Medical School, Macquarie University, Abstract: Microglial cell processes form part of a subset of synaptic contacts that have been dubbed microglial tetra-partite or quad-partite synapses
This process could be reversed by the addition of 2DG, which resulted in the inhibition of HIF-1α accumulation and IL-1β production, and rescued long-term potentiation (LTP) of synaptic plasticity
Since tetrapartite may refer to the presence of extracellular matrix components, we propose the more precise term microglial penta-partite synapse for synaptic contacts that show a microglial cell process in close physical proximity to neuronal and astrocytic synaptic elements
Summary
The ability to adapt and protect neuronal circuitry throughout an animal’s lifespan is a remarkable feature of the CNS. York et al [23] reported metabolic reprogramming of microglia stimulated by lipopolysaccharide (LPS), which resulted in glycolysis necessary for IL1β production This process could be reversed by the addition of 2DG, which resulted in the inhibition of HIF-1α accumulation and IL-1β production, and rescued long-term potentiation (LTP) of synaptic plasticity. Overall, microglia and their cytokines are recognised to play an indispensable role in plasticity of the tetra-partite synapse. Since tetrapartite may refer to the presence of extracellular matrix components, we propose the more precise term microglial penta-partite synapse for synaptic contacts that show a microglial cell process in close physical proximity to neuronal and astrocytic synaptic elements. We propose instead that dysfunction of the microglial penta-partite synapse is of key relevance to CNS disorders that feature microglial activation
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