Microglial dynamics

Microglial cells are “the first line of defense” of mammalian brain.

The tiny processes of “resting” microglia are restlessly moving, surveying every corner of brain parenchyma. They quickly react to micro-lesions by surrounding a broken capillary or an apoptotic neuron and cleaning up the debris.

During ageing or inflammation, microglia lose their ability to extend processes towards the lesions site; their morphology changes dramatically, they become activated and start migrating.

Neurotar’s microglial imaging assays offer a variety of readouts, such as quantification of motility rate of microglial processes, kinetic analysis of their extension towards laser-induced microlesions, changes in cell morphology (cell soma size, process branching) and migration under inflammatory conditions, and co-localization of fluorescently-tagged molecules (e.g., BBB-penetrating antibodies) with microglia and their sub-cellular organelles (e.g., lysosomes).

Study design

  • 2-5 groups, e.g., 1 placebo, 1-2 test compounds and optionally 1 positive control and/or 1 negative control
  • 3-5 imaging sessions: baseline -24 h, 0 h,  optionally 6 h, 24 h, optionally 72 h,  optionally 144 h
  • 1-3 imaging areas per animal
  • 2-3 microlesions induced per imaging area per time point
  • report delivered 2-4 months after the study commencement

Options and extensions

  • Different drug administration routs: per oral (gavage), injections i.p., s.c., i.v. or i.t. (intrathecal)
  • Can be combined with PK measurements for biologics targeting/affecting microglia

Papers

  • Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, et al. (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. 8(6):752–8. 10.1038/nn1472
  • Hefendehl J.K., Neher J.J., Suhs R.B., Kohsaka S., Skodras A., Jucker M. (2014) Homeostatic and injury-induced microglia behavior in the aging brain. Aging Cell. 13:60–69. 10.1111/acel.12149 
  • Gyoneva S., Davalos D., Biswas D., Swanger S. A., Garnier-Amblard E., Loth F., et al. (2014). Systemic inflammation regulates microglial responses to tissue damage in vivo. Glia 62:1345–1360. 10.1002/glia.22686 
  • Sipe G. O., Lowery R. L., Tremblay M. E., Kelly E. A., Lamantia C. E., Majewska A. K. (2016). Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex. Nat. Commun. 7:10905 10.1038/ncomms10905
  • Lou N, et al. Purinergic receptor P2RY12-dependent microglial closure of the injured blood-brain barrier. (2016)  PNAS USA. 113(4):1074–1079. 10.1073/pnas.1520398113 
  • Miyamoto A., Wake H., Ishikawa A. W., Eto K., Shibata K., Murakoshi H., et al. (2016). Microglia contact induces synapse formation in developing somatosensory cortex. Nat. Commun. 7:12540 10.1038/ncomms12540