Matrix-Microglia interactions


KEYWORDS

  • Extracellular matrix

  • Microglia

  • Aging


TECHNIQUES

  • 2-photon microscopy

  • Confocal microscopy

  • 3D-in vitro cultures

  • Immunofluorescence

  • Script-assisted image analysis


How does the extracellular matrix influences microglial motility?

Beyond neurons and glia, the Central Nervous System (CNS) holds a plastic scaffold known as the extracellular matrix (ECM). Unlike the ECM from connective tissue, where collagen is the main unit, the neural interstitial matrix consists mostly on long chains of the glycan polymer hyaluronan. Protein components of the ECM bind to hyaluronan forming a self-assembled matrix that functions as structural framework and signalling hub. Microglia, the never-resting immune cell of the CNS, constantly surveys the brain parenchyma, interacting with neighbouring cells and the surrounding extracellular microenvironment. Despite recent insights on matrix-glia interplay (Soria et al., 2020, Nat Commun; Nguyen et al., 2020, Cell), it is unknown whether changes in the structural matrix affect microglial motility. Here we aim to unravel whether the matrix influences microglia physiology, and conversely, whether microglia modulates hyaluronan status.

Funded by Basque Government and Ministerio de Ciencia e Innovación

2-photon time-lapse of microglia reacting to a laser lesion, in acute brain slices of Cx3Cr1-eGFP/+ mice


Does aging impact on matrix-glia interplay?

Neurological disorders are a growing cause of mortality and leading cause of disability worldwide, carrying great socio-economic burden and impairing the elderly life of millions. The outstanding scientific achievements from recent decades have extended our life expectancy considerably, stretching the lifespan of the population and therefore the incidence of age-related pathologies, especially brain disorders. Hence, there is an increasing need to study the physiology of the aging brain, to understand not only the etiology of neurological disorders, but also how aging cells respond to injury. Despite hyaluronan accumulation in aging and proven effect of matrix stiffness on the physiology, motility and migration of brain cells, it is unknown whether age-related changes in the structural matrix affect microglial function. In this context, we aim to explore whether matrix-microglia interactions are altered in aging and in age-related pathologies.

Hyaluronan accumulation in mice during aging

Publications related to this topic

  • Soria FN, Paviolo C, Doudnikoff E, Arotcarena M-L, Lee A, Danné N, Mandal AK, Gosset P, Dehay B, Groc L, Cognet L, Bezard E. Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling. Nat Commun 2020; 11: 3440. [LINK]

  • Soria FN, Miguelez C, Peñagarikano O, Tønnesen J. Current Techniques for Investigating the Brain Extracellular Space. Front Neurosci 2020; 14: 570750. [LINK]