Microglia morphophysiological diversity and its implications for the CNS

Vidal-Itriago, Andrés; Radford, Rowan A. W.; Aramideh, Jason Abbas; Maurel, Cindy; Scherer, Natalie M.; Don, Emily K.; Lee, Albert; Chung, Roger S.; Graeber, Manuel B.; Morsch, Marco

doi:10.3389/fimmu.2022.997786

Cited by 142 publications

(73 citation statements)

References 162 publications

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“…Morphologically, microglia are very diverse and dynamic [ 325 ]. In the healthy brain, microglial cells often display a highly ramified morphology with many processes.…”

Section: Primer On Microglia: Never-resting Brain “Police” With the M...mentioning

confidence: 99%

Synapse Dysfunctions in Multiple Sclerosis

Schwarz

Schmitz

2023

IJMS

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Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system (CNS) affecting nearly three million humans worldwide. In MS, cells of an auto-reactive immune system invade the brain and cause neuroinflammation. Neuroinflammation triggers a complex, multi-faceted harmful process not only in the white matter but also in the grey matter of the brain. In the grey matter, neuroinflammation causes synapse dysfunctions. Synapse dysfunctions in MS occur early and independent from white matter demyelination and are likely correlates of cognitive and mental symptoms in MS. Disturbed synapse/glia interactions and elevated neuroinflammatory signals play a central role. Glutamatergic excitotoxic synapse damage emerges as a major mechanism. We review synapse/glia communication under normal conditions and summarize how this communication becomes malfunctional during neuroinflammation in MS. We discuss mechanisms of how disturbed glia/synapse communication can lead to synapse dysfunctions, signaling dysbalance, and neurodegeneration in MS.

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“…Morphologically, microglia are very diverse and dynamic [ 325 ]. In the healthy brain, microglial cells often display a highly ramified morphology with many processes.…”

Section: Primer On Microglia: Never-resting Brain “Police” With the M...mentioning

confidence: 99%

Synapse Dysfunctions in Multiple Sclerosis

Schwarz

Schmitz

2023

IJMS

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“…Microglia constantly remove damaged nerves, plaques, and infectious substances from the CNS. Activated microglia play an important role in neurodegenerative diseases such as Parkinson’s disease, multiple sclerosis, and Alzheimer’s disease ( 67 ). Microglia are activated soon after initial damage in the spinal cord.…”

Section: How Are the Functions Of Immune Cells And Immune Factors Orc...mentioning

confidence: 99%

“…Cytokines and chemokines released by activated microglia can induce leukocytes and macrophages to release inflammatory factors and cytotoxic substances, mediating neuroinflammation and neurotoxicity. This leads to the destruction of the BBB, and causes glial cell death ( 67 ). Recently, cytokines released by activated microglia after CNS injury occurrence have been found to influence the neurotoxic or neuroprotective effects of astrocytes ( 39 ).…”

Section: How Are the Functions Of Immune Cells And Immune Factors Orc...mentioning

confidence: 99%

The role of immune cells and associated immunological factors in the immune response to spinal cord injury

Tang¹,

Gu²,

Jiang³

et al. 2023

Front. Immunol.

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Spinal cord injury (SCI) is a devastating neurological condition prevalent worldwide. Where the pathological mechanisms underlying SCI are concerned, we can distinguish between primary injury caused by initial mechanical damage and secondary injury characterized by a series of biological responses, such as vascular dysfunction, oxidative stress, neurotransmitter toxicity, lipid peroxidation, and immune-inflammatory response. Secondary injury causes further tissue loss and dysfunction, and the immune response appears to be the key molecular mechanism affecting injured tissue regeneration and functional recovery from SCI. Immune response after SCI involves the activation of different immune cells and the production of immunity-associated chemicals. With the development of new biological technologies, such as transcriptomics, the heterogeneity of immune cells and chemicals can be classified with greater precision. In this review, we focus on the current understanding of the heterogeneity of these immune components and the roles they play in SCI, including reactive astrogliosis and glial scar formation, neutrophil migration, macrophage transformation, resident microglia activation and proliferation, and the humoral immunity mediated by T and B cells. We also summarize findings from clinical trials of immunomodulatory therapies for SCI and briefly review promising therapeutic drugs currently being researched.

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“…Microglial activity can be reflected in their morphology (Savage, Carrier et al 2019, Vidal-Itriago, Radford et al 2022). Specifically, "surveilling" microglia assume a more ramified morphology, while "effector" microglia deviate from this morphology (e.g., ameboid, hyper-ramified, etc.)…”

Section: Methamphetamine Administration Induces Lasting Changes In Th...mentioning

confidence: 99%

Microglia contribute to methamphetamine reinforcement and reflect persistent transcriptional and morphological adaptations to the drug

Vilca,

Margetts,

Fleites

et al. 2023

Preprint

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Methamphetamine use disorder (MUD) is a chronic, relapsing disease that is characterized by repeated drug use despite negative consequences and for which there are currently no FDA approved cessation therapeutics. Repeated methamphetamine (METH) use induces long-term gene expression changes in brain regions associated with reward processing and drug-seeking behavior, and recent evidence suggests that methamphetamine-induced neuroinflammation may also shape behavioral and molecular responses to the drug. Microglia, the resident immune cells in the brain, are principal drivers of neuroinflammatory responses and contribute to the pathophysiology of substance use disorders. Here, we investigated transcriptional and morphological changes in striatal microglia in response to methamphetamine-taking and during methamphetamine abstinence, as well as their functional contribution to drug-taking behavior. We show that methamphetamine self-administration induces transcriptional changes related to protein folding, mRNA processing, immune signaling, and neurotransmission in striatal microglia. Importantly, many of these transcriptional changes persist through abstinence, a finding supported by morphological analysis. Functionally, we report that microglial ablation increases methamphetamine-taking, possibly involving neuroimmune and neurotransmitter regulation. In contrast, microglial depletion did not alter methamphetamine-seeking behavior following 21 days of abstinence, highlighting the complexity of drug-seeking behaviors. Taken together, these results suggest that methamphetamine induces both short and long-term changes in striatal microglia that contribute to altered drug-taking behavior and may be leveraged for preclinical development of methamphetamine cessation therapeutics.

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Microglia morphophysiological diversity and its implications for the CNS

Cited by 142 publications

References 162 publications

Synapse Dysfunctions in Multiple Sclerosis

Synapse Dysfunctions in Multiple Sclerosis

The role of immune cells and associated immunological factors in the immune response to spinal cord injury

Microglia contribute to methamphetamine reinforcement and reflect persistent transcriptional and morphological adaptations to the drug

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