Abstract
BackgroundMicroglia cells are the resident macrophages of the central nervous system and are considered its first line of defense. In the normal brain, their ramified processes are highly motile, constantly scanning the surrounding brain tissue and rapidly moving towards sites of acute injury or danger signals. These microglial dynamics are thought to be critical for brain homeostasis. Under pathological conditions, microglial cells undergo “activation,” which modifies many of their molecular and morphological properties. Investigations of the effects of activation on motility are limited and have given mixed results. In particular, little is known about how microglial motility is altered in epilepsy, which is characterized by a strong inflammatory reaction and microglial activation.MethodsWe used a mouse model of status epilepticus induced by kainate injections and time-lapse two-photon microscopy to image GFP-labeled microglia in acute hippocampal brain slices. We studied how microglial activation affected the motility of microglial processes, including basal motility, and their responses to local triggering stimuli.ResultsOur study reveals that microglial motility was largely preserved in kainate-treated animals, despite clear signs of microglial activation. In addition, whereas the velocities of microglial processes during basal scanning and towards a laser lesion were unaltered 48 h after status epilepticus, we observed an increase in the size of the territory scanned by single microglial processes during basal motility and an elevated directional velocity towards a pipette containing a purinergic agonist.ConclusionsMicroglial activation differentially impacted the dynamic scanning behavior of microglia in response to specific acute noxious stimuli, which may be an important feature of the adaptive behavior of microglia during pathophysiological conditions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-015-0421-6) contains supplementary material, which is available to authorized users.
Highlights
Microglia cells are the resident macrophages of the central nervous system and are considered its first line of defense
We checked whether the degree of morphological changes after status epilepticus (SE) induction correlated with the severity of SE, as classified according to a modified Racine scale
We observed that the basal velocity of microglial processes and their directional motility towards a laser lesion were unaffected, while the size of the territory scanned by individual microglial processes and their velocity towards a source of adenosine triphosphate (ATP) analogs were markedly increased after the induction of SE
Summary
Microglia cells are the resident macrophages of the central nervous system and are considered its first line of defense. Their ramified processes are highly motile, constantly scanning the surrounding brain tissue and rapidly moving towards sites of acute injury or danger signals. These microglial dynamics are thought to be critical for brain homeostasis. In response to an acute lesion, microglia rapidly project their processes towards sites of danger signals (called directional motility; [3, 4, 9]), presumably to probe and contain the damage and to protect the surrounding cells [10]. Avignone et al Journal of Neuroinflammation (2015) 12:202 Due to their role as immune-competent cells, a variety of signals are expected to attract microglial processes. Extracellular ATP affects basal motility [3, 12], while activation of purinergic P2Y12 receptors (P2Y12R) mediates directional motility induced by laser lesions [13, 14]
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