Microglial modulation of neuronal activity in the healthy brain

York, Elisa M.; Bernier, Louis‐Philippe; MacVicar, Brian A.

doi:10.1002/dneu.22571

Cited by 87 publications

(79 citation statements)

References 100 publications

(139 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to perform these above‐mentioned functions a diverse array of receptors including TAM receptors, glutamate receptors, and purinergic receptors are used by microglia to efficiently communicate with other cells (Fourgeaud et al, ; York, Bernier, & MacVicar, ). Among these complex systems the CX3CL1/CX3CR1 and CD200‐CD200R axes play key roles in microglia–neuron contact (Eyo & Wu, ; Kierdorf & Prinz, ; Limatola & Ransohoff, ; Mecca, Giambanco, Donato, & Arcuri, ).…”

Section: Multi‐tasking Microglia: a Friend For Brain Homeostasismentioning

confidence: 99%

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

Han

Zhu

Zhang

et al. 2018

Glia

View full text Add to dashboard Cite

Microglia are prominent immune cells in the central nervous system (CNS) and are critical players in both neurological development and homeostasis, and in neurological diseases when dysfunctional. Our previous understanding of the phenotypes and functions of microglia has been greatly extended by a dearth of recent investigations. Distinct genetically defined subsets of microglia are now recognized to perform their own independent functions in specific conditions. The molecular profiling of single microglial cells indicates extensively heterogeneous reactions in different neurological disorders, resulting in multiple potentials for crosstalk with other kinds of CNS cells such as astrocytes and neurons. In settings of neurological diseases it could thus be prudent to establish effective cell‐based therapies by targeting entire microglial networks. Notably, activated microglial depletion through genetic targeting or pharmacological therapies within a suitable time window can stimulate replenishment of the CNS niche with new microglia. Additionally, enforced repopulation through provision of replacement cells also represents a potential means of exchanging dysfunctional with functional microglia. In each setting the newly repopulated microglia might have the potential to resolve ongoing neuroinflammation. In this review, we aim to summarize the most recent knowledge of microglia and to highlight microglial depletion and subsequent repopulation as a promising cell replacement therapy. Although glial cell replacement therapy is still in its infancy and future translational studies are still required, the approach is scientifically sound and provides new optimism for managing the neurotoxicity and neuroinflammation induced by activated microglia.

show abstract

Section: Multi‐tasking Microglia: a Friend For Brain Homeostasismentioning

confidence: 99%

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

Han

Zhu

Zhang

et al. 2018

Glia

View full text Add to dashboard Cite

show abstract

“…Although microglia and astrocytes are master regulators of the central immune system, mounting evidence demonstrates that they influence processes beyond inflammation and immune surveillance. These cells actively regulate synaptic glutamate spillover, activity‐dependent synaptogenesis and elimination, neuronal morphology, neurotransmitter synthesis, synaptic connectivity, and neural circuit function (Scofield & Kalivas, ; Guerra‐Gomes et al ., ; York et al ., ). These functions of glial cells are significantly altered by exposure to abused drugs, and such changes likely contribute to the behavioral outcomes associated with substance abuse (Miguel‐Hidalgo, ; Coller & Hutchinson, ).…”

Section: Introductionmentioning

confidence: 99%

“…These cells actively regulate synaptic glutamate spillover, activitydependent synaptogenesis and elimination, neuronal morphology, neurotransmitter synthesis, synaptic connectivity, and neural circuit function Guerra-Gomes et al, 2017;York et al, 2017). These functions of glial cells are significantly altered by exposure to abused drugs, and such changes likely contribute to the behavioral outcomes associated with substance abuse (Miguel-Hidalgo, 2009;Coller & Hutchinson, 2012).…”

Section: Introductionmentioning

confidence: 99%

Glial mechanisms underlying substance use disorders

Linker

Cross

Leslie

2018

Eur J of Neuroscience

View full text Add to dashboard Cite

Addiction is a devastating disorder that produces persistent maladaptive changes to the central nervous system, including glial cells. Although there is an extensive body of literature examining the neuronal mechanisms of substance use disorders, effective therapies remain elusive. Glia, particularly microglia and astrocytes, have an emerging and meaningful role in a variety of processes beyond inflammation and immune surveillance, and may represent a promising therapeutic target. Indeed, glia actively modulate neurotransmission, synaptic connectivity and neural circuit function, and are critically poised to contribute to addictive‐like brain states and behaviors. In this review, we argue that glia influence the cellular, molecular, and synaptic changes that occur in neurons following drug exposure, and that this cellular relationship is critically modified following drug exposure. We discuss direct actions of abused drugs on glial function through immune receptors, such as Toll‐like receptor 4, as well as other mechanisms. We highlight how drugs of abuse affect glia‐neural communication, and the profound effects that glial‐derived factors have on neuronal excitability, structure, and function. Recent research demonstrates that glia have brain region‐specific functions, and glia in different brain regions have distinct contributions to drug‐associated behaviors. We will also evaluate the evidence demonstrating that glial activation is essential for drug reward and drug‐induced dopamine release, and highlight clinical evidence showing that glial mechanisms contribute to drug abuse liability. In this review, we synthesize the extensive evidence that glia have a unique, pivotal, and underappreciated role in the development and maintenance of addiction.

show abstract

“…Neuronal survival and normal function may be affected by cellular changes that are internal to them. However, neurons are highly dependent on glia for many reasons (York et al ). Therefore, the aging of glia can have significant impact on neuronal viability as well as the proteins they express or even protein turn‐over (Brown ; Verkhratsky et al ).…”

mentioning

confidence: 99%

Microglia and the aging brain: are senescent microglia the key to neurodegeneration?

Angelova

Brown

2019

Journal of Neurochemistry

181

125

View full text Add to dashboard Cite

The single largest risk factor for etiology of neurodegenerative diseases like Alzheimer’s disease is increased age. Therefore, understanding the changes that occur as a result of aging is central to any possible prevention or cure for such conditions. Microglia, the resident brain glial population most associated with both protection of neurons in health and their destruction is disease, could be a significant player in age related changes. Microglia can adopt an aberrant phenotype sometimes referred to either as dystrophic or senescent. While aged microglia have been frequently identified in neurodegenerative diseases such as Alzheimer’s disease, there is no conclusive evidence that proves a causal role. This has been hampered by a lack of models of aged microglia. We have recently generated a model of senescent microglia based on the observation that all dystrophic microglia show iron overload. Iron‐overloading cultured microglia causes them to take on a senescent phenotype and can cause changes in models of neurodegeneration similar to those observed in patients. This review considers how this model could be used to determine the role of senescent microglia in neurodegenerative diseases.

show abstract

Microglial modulation of neuronal activity in the healthy brain

Cited by 87 publications

References 100 publications

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

Glial mechanisms underlying substance use disorders

Microglia and the aging brain: are senescent microglia the key to neurodegeneration?

Contact Info

Product

Resources

About