Elena Avignone, Valentin Nägerl dans J Neuroinflammation

Modification de la dynamique des prolongements microgliaux après l’induction d’une crise d’épilepsie de type grand mal (status epilepticus)

Altered morphological dynamics of activated microglia after induction of status epilepticus.
Avignone E, Lepleux M, Angibaud J, Nägerl UV. J Neuroinflammation. 2015 Nov 4;12(1):202. doi: 10.1186/s12974-015-0421-6.

Since a decade we know that in physiological conditions microglia move constantly their processes (called basal motility) scanning the surrounding brain tissue, and that in response to an acute lesion they can rapidly project their processes towards sites of danger signals (called directional motility). Motility is thought to be a key factor in the homeostasis control exerted by microglia, presumably probing and containing the damage to protect the surrounding cells. However whether microglia can maintain these functions intact in pathological conditions remained an open and key question.

Few years ago, in the lab of Etienne Audinat we characterized how microglial cells change their properties after the induction of status epilepticus. Thanks to the Chaire d’Excellence de l’Université de Bordeaux and CNRS, I further explored this topic when I joined the Institut Interdisciplinaire de Neuroscience (Synaptic plasticity and super-resolution microscopy group). We used GFP-labeled microglia and two photon microscopy to characterize in detail how this specific pathological condition affects microglial motility.

Our results show that 48 hours after status epilepticus microglial processes were able to scan a larger territory without changing their velocity. Furthermore the processes motility towards a specific site was differently modulated according to the trigger stimulus. While the directional motility towards a small lesion induced by a laser was not affected, processes moved at double speed towards a source of an ATP analogue (considered an alerting signal).

Thus although some of properties of microglia dramatically changed after the induction of status epilepcticus, its motility is not compromised. Indeed, they can still patrol the environment and react to stimuli, possibly even in a more efficient way. This study also reveals us that motility cannot be considered as a single phenomenon, but each type of motility can be differently affected by diverse pathological conditions, suggesting that they may have a different role. The overall role and properties of microglia likely change along lifespan, from the immature to mature brain, but that’s another ongoing story…

Figure legend: Changes of microglial dynamics in the hippocampus after status epilepticus. Two photon images of microglial cells at two different time points during basal motility (left) and directional motility (right) in control (top) and in hippocampal slices from animal 48h after status epilepticus. After status epilepticus, microglial processes explore a larger territory during basal motility, as indicated by the retracting (red) and expanding (green) movements (scale bar 5µm). In response to a danger signal represented by an ATP analogue (yellow clue), they increase their velocity towards the target, arriving and surrounding the site more rapidly (scale bar 15µm).