Interactions of glial cells with neuronal synapses, from astrocytes to microglia and oligodendrocyte lineage cells

Liu, Yao; Shen, Xi; Zhang, Yuhan; Zheng, Xiaoli; Cepeda, Carlos; Wang, Yao; Duan, Shumin; Tong, Xiaoping

doi:10.1002/glia.24343

Cited by 38 publications

(23 citation statements)

References 180 publications

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“…Microglia interact with neurons through synaptic pruning to shape synapse formation and synaptic transmission ( 20, 21 ). We thus examined the impact of AUD HPRS and LPRS microglial cells on human iPSC-derived neurons.…”

Section: Resultsmentioning

confidence: 99%

Polygenic Risk for Alcohol Use Disorder Affects Cellular Responses to Ethanol Exposure in a Human Microglial Cell Model

Li,

Liu,

Boreland

et al. 2024

Preprint

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Polygenic risk scores (PRS) assess genetic susceptibility to Alcohol Use Disorder (AUD), yet their molecular implications remain underexplored. Neuroimmune interactions, particularly in microglia, are recognized as significant contributors to AUD pathophysiology. We investigated the interplay between AUD PRS and ethanol in human microglia derived from iPSCs from individuals with high- or low-PRS (HPRS or LPRS) of AUD. Ethanol exposure induced elevated CD68 expression and morphological changes in microglia, with differential responses between HPRS and LPRS microglial cells. Transcriptomic analysis revealed expression differences in MHCII complex and phagocytosis-related genes following ethanol exposure; HPRS microglial cells displayed enhanced phagocytosis and increasedCLEC7Aexpression, unlike LPRS microglial cells. Synapse numbers in co-cultures of induced neurons with microglia after alcohol exposure were lower in HRPS co-cultures, suggesting possible excess synapse pruning. This study provides insights into the intricate relationship between AUD PRS, ethanol, and microglial function, potentially influencing neuronal functions in developing AUD.

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Section: Resultsmentioning

confidence: 99%

Polygenic Risk for Alcohol Use Disorder Affects Cellular Responses to Ethanol Exposure in a Human Microglial Cell Model

Li,

Liu,

Boreland

et al. 2024

Preprint

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“…Oligodendrocytes and oligodendrocyte precursor cells (OPCs) have functions for synapses that are only gradually understood (31, 32). Recently, OPCs have been shown to be involved in synapse elimination (33, 34).…”

Section: Discussionmentioning

confidence: 99%

Developmental oligodendrocytes regulate brain function through the mediation of synchronized spontaneous activity

Masumura,

Goda,

Sekiguchi

et al. 2024

Preprint

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Immature animals have the ability to interact with their environment, indicating that complex neural circuits are formed through mechanisms of self-organization. Correlated spontaneous activity among neurons suggests a universal principle behind the self-organization of complex neural circuits1,2, though the underlying mechanisms and functional roles in the central nervous system remain unclear. Here, we show that oligodendrocyte-dependent synchronized spontaneous activity during the critical period is indispensable for neural circuit refinement and brain functionalization. We found that oligodendrocyte deletion during specific time window disrupts Purkinje cell activity synchrony and synapse elimination in the mouse cerebellum. We further demonstrated that synchronized spontaneous activity is a prerequisite for synapse elimination. Behavioral analyses linked these developmental disruptions to adult cerebellar function, manifesting as anxiety-like behavior, reduced social interaction, and compromised motor coordination in adult mice. This association indicates the significance of following the appropriate developmental trajectory to ensure the integrity of brain function, suggesting that oligodendrocytes during development are vital organizers of brain functionalization. Our findings highlight the crucial role of oligodendrocytes in orchestrating synapse elimination and optimizing brain function through the mediation of synchronized activity during specific developmental stages.

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“…These findings may have only been identified due to glial processes being present in synaptoneurosomes. This is important because glia are known to utilize the complement cascade at the synapse to instigate phagocytosis of synapses, which is known to be increased in neurodegeneration ( Henstridge et al, 2019 ; Dalakas et al, 2020 ; Liu et al, 2023 ). This highlights the importance of considering the physiological differences between synaptosomes and synaptoneurosomes when investigating dysregulated pathological synaptic pathways.…”

Section: Studying Synapses At the Molecular Levelmentioning

confidence: 99%

Bringing synapses into focus: Recent advances in synaptic imaging and mass-spectrometry for studying synaptopathy

Hindley

Avila

Henstridge

2023

Front. Synaptic Neurosci.

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Synapses are integral for healthy brain function and are becoming increasingly recognized as key structures in the early stages of brain disease. Understanding the pathological processes driving synaptic dysfunction will unlock new therapeutic opportunities for some of the most devastating diseases of our time. To achieve this we need a solid repertoire of imaging and molecular tools to interrogate synaptic biology at greater resolution. Synapses have historically been examined in small numbers, using highly technical imaging modalities, or in bulk, using crude molecular approaches. However, recent advances in imaging techniques are allowing us to analyze large numbers of synapses, at single-synapse resolution. Furthermore, multiplexing is now achievable with some of these approaches, meaning we can examine multiple proteins at individual synapses in intact tissue. New molecular techniques now allow accurate quantification of proteins from isolated synapses. The development of increasingly sensitive mass-spectrometry equipment means we can now scan the synaptic molecular landscape almost in totality and see how this changes in disease. As we embrace these new technical developments, synapses will be viewed with clearer focus, and the field of synaptopathy will become richer with insightful and high-quality data. Here, we will discuss some of the ways in which synaptic interrogation is being facilitated by methodological advances, focusing on imaging, and mass spectrometry.

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Interactions of glial cells with neuronal synapses, from astrocytes to microglia and oligodendrocyte lineage cells

Cited by 38 publications

References 180 publications

Polygenic Risk for Alcohol Use Disorder Affects Cellular Responses to Ethanol Exposure in a Human Microglial Cell Model

Polygenic Risk for Alcohol Use Disorder Affects Cellular Responses to Ethanol Exposure in a Human Microglial Cell Model

Developmental oligodendrocytes regulate brain function through the mediation of synchronized spontaneous activity

Bringing synapses into focus: Recent advances in synaptic imaging and mass-spectrometry for studying synaptopathy

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