Distinguishing the effects of systemic CSF1R inhibition by PLX3397 on microglia and peripheral immune cells.

Microglia, the primary immune cells of the central nervous system (CNS), are derived from the yolk sac and populate the brain during development. Once microglia migrate to the CNS, they are self-renewing and require CSF1R signaling for their maintenance. Pexidartinib (PLX3397, PLX), a small molecule inhibitor of the CSF1R, has been shown to effectively deplete microglia since microglial maintenance is CSF1R-dependent.

Microglia play beneficial roles in multiple experimental seizure models.

Seizure disorders are common, affecting both the young and the old. Currently available antiseizure drugs are ineffective in a third of patients and have been developed with a focus on known neurocentric mechanisms, raising the need for investigations into alternative and complementary mechanisms that contribute to seizure generation or its containment. Neuroinflammation, broadly defined as the activation of immune cells and molecules in the central nervous system (CNS), has been proposed to facilitate seizure generation, although the specific cells involved in these processes remain inadequately understood.

Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice.

Microglia are brain-resident immune cells with a repertoire of functions in the brain. However, the extent of their interactions with the vasculature and potential regulation of vascular physiology has been insufficiently explored. Here, we document interactions between ramified CX3CR1 myeloid cell somata and brain capillaries.

Negative feedback control of neuronal activity by microglia.

Microglia, the brain's resident macrophages, help to regulate brain function by removing dying neurons, pruning non-functional synapses, and producing ligands that support neuronal survival. Here we show that microglia are also critical modulators of neuronal activity and associated behavioural responses in mice. Microglia respond to neuronal activation by suppressing neuronal activity, and ablation of microglia amplifies and synchronizes the activity of neurons, leading to seizures.

A decade of diverse microglial-neuronal physical interactions in the brain (2008-2018).

Microglia are unique cells of the central nervous system (CNS) with a distinct ontogeny and molecular profile. They are the predominant immune resident cell in the CNS. Recent studies have revealed a diversity of transient and terminal physical interactions between microglia and neurons in the vertebrate brain.