Microglia-neuron crosstalk: Signaling mechanism and control of synaptic transmission

Marinelli, Silvia; Basilico, Bernadette; Marrone, Maria Cristina; Ragozzino, Davide

doi:10.1016/j.semcdb.2019.05.017

Cited by 158 publications

(125 citation statements)

References 233 publications

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“…Few studies have examined the transcriptional changes of signaling molecules implicated in microglial-neuronal interactions, such as the fractalkine (CX3CL1)/fractalkine receptor (CX3CR1) system, the CD200/CD200R system, and the P2Y purinergic receptor 12 (P2Y12) [21,22].…”

Section: Early-life Stress and Microglia: Preclinical Studiesmentioning

confidence: 99%

Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development

Catale

Gironda

Iacono

et al. 2020

JCM

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The putative effects of early-life stress (ELS) on later behavior and neurobiology have been widely investigated. Recently, microglia have been implicated in mediating some of the effects of ELS on behavior. In this review, findings from preclinical and clinical literature with a specific focus on microglial alterations induced by the exposure to ELS (i.e., exposure to behavioral stressors or environmental agents and infection) are summarized. These studies were utilized to interpret changes in developmental trajectories based on the time at which the stress occurred, as well as the paradigm used. ELS and microglial alterations were found to be associated with a wide array of deficits including cognitive performance, memory, reward processing, and processing of social stimuli. Four general conclusions emerged: (1) ELS interferes with microglial developmental programs, including their proliferation and death and their phagocytic activity; (2) this can affect neuronal and non-neuronal developmental processes, which are dynamic during development and for which microglial activity is instrumental; (3) the effects are extremely dependent on the time point at which the investigation is carried out; and (4) both pre- and postnatal ELS can prime microglial reactivity, indicating a long-lasting alteration, which has been implicated in behavioral abnormalities later in life.

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Section: Early-life Stress and Microglia: Preclinical Studiesmentioning

confidence: 99%

Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development

Catale

Gironda

Iacono

et al. 2020

JCM

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“…While experiments focused on examining in vitro iMG functions such as migration, phagocytosis, and inflammatory responses represent straightforward and high‐throughput paradigms that are easy to interpret, they neglect the reality of the brain environment in which microglia interact with neurons, astrocytes, oligodendrocytes, endothelial cells, and infiltrating peripheral immune cells. Growing evidence has demonstrated the considerable interplay between microglia and astrocyte signaling (Liddelow et al, ) and likewise the neuronal regulation of microglia activation state is well‐established (Marinelli, Basilico, Marrone, & Ragozzino, ; Sheridan & Murphy, ). More recently, interactions between vascular endothelial cells and microglia have been implicated in aging, AD, and stroke (Dudvarski Stankovic, Teodorczyk, Ploen, Zipp, & Schmidt, ; Merlini et al, ; Yousef et al, ).…”

Section: Benefits and Limitationsmentioning

confidence: 99%

Human iPSC‐derived microglia: A growing toolset to study the brain's innate immune cells

Hasselmann

Blurton‐Jones

2020

Glia

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Recent advances in the generation of microglia from human induced pluripotent stem cells (iPSCs) have provided exciting new approaches to examine and decipher the biology of microglia. As these techniques continue to evolve to encompass more complex in situ and in vivo paradigms, so too have they begun to yield novel scientific insight into the genetics and function of human microglia. As such, researchers now have access to a toolset comprised of three unique “flavors” of iPSC‐derived microglia: in vitro microglia (iMGs), organoid microglia (oMGs), and xenotransplanted microglia (xMGs). The goal of this review is to discuss the variety of research applications that each of these techniques enables and to highlight recent discoveries that these methods have begun to uncover. By presenting the research paradigms in which each model has been successful, as well as the key benefits and limitations of each approach, it is our hope that this review will help interested researchers to incorporate these techniques into their studies, collectively advancing our understanding of human microglia biology.

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“…In vivo imaging studies have demonstrated the dynamic interaction of microglia with synapses in the mouse cortex (microglia frequently but transiently contact synaptic spines and terminals), 69 where microglia rapidly respond to cues of neural activity and neurotransmitter release. [70][71][72] These interactions are significantly prolonged following ischemic stroke and are associated with subsequent synaptic elimination. 69 Microglia actively phagocytose synapses that need to be eliminated.…”

Section: Neuron-microglia Crosstalk In Strokementioning

confidence: 99%

Potential microglia‐based interventions for stroke

Huang

Yang

et al. 2020

CNS Neurosci Ther

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A large number of families worldwide suffer from the physical and mental burden posed by stroke. An increasing number of studies aimed at the prevention and treatment of stroke have been conducted. Specifically, manipulating the immune response to stroke is under intense investigation. Microglia are the principal immune cells in the brain and are the first line of defense against the pathophysiology induced by stroke. Increasing evidence has suggested that microglia play diverse roles that depend on dynamic interactions with neurons, astrocytes, and other neighboring cells both in the normal brain and under pathological conditions, including stroke. Moreover, there are dynamic alterations in microglial functions with respect to aging and sex differences in the human brain, which offer a deep understanding of the conditions of stroke patients of different ages and sex. Hence, we review the dynamic microglial reactions caused by aging, sex, and crosstalk with neighboring cells both in normal conditions and after stroke and relevant potential interventions.

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Microglia-neuron crosstalk: Signaling mechanism and control of synaptic transmission

Cited by 158 publications

References 233 publications

Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development

Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development

Human iPSC‐derived microglia: A growing toolset to study the brain's innate immune cells

Potential microglia‐based interventions for stroke

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