Microglia-neuron and microglia-vascular interactions

Microglia are the major immune cells of the brain and the main regulators of inflammatory processes in the central nervous system. At the same time, a growing body of research data shows that microglia are of paramount importance in the physiological functioning of the developing nervous system and the adult brain. It is therefore important to gain a comprehensive understanding of the molecular anatomy and molecular mechanisms of the complex interactions formed by microglia in order to understand the pathophysiology of neurodegenerative diseases and to develop new and effective therapeutic approaches. Our research group has identified several specific types of interactions of microglia with neurons and cerebral blood vessels, through which microglia regulate neuronal activity, injury, and cerebral circulation in health and disease (e.g. Szalay et al., Nature Communications 2016, Cserép et al. Science 2020, Császár et al., J Exp Med 2022). Our research includes confocal-, superresolution- and electron microscopy, 3D contactomics, in vivo imaging (laser speckle contrast imaging, in vivo two-photon microscopy, functional ultrasound, etc.), ex vivo methods (glial and neuronal cultures, acute or organotypic slices, biosensors, ex vivo time lapse imaging, flow cytometry, etc.) and other methods to identify microglial interactions with neurons and vascular structures, and reveal the receptors and mediators involved with their functional roles identified. We will pay particular attention to the translation of our results into possible clinical benefit, and therefore devote increasing attention to validating mouse data in post-mortem human brain samples.

Our selected papers on this topic:

Császár, E., Lénárt, N., Cserép, C., Környei, Z., Fekete, R., Pósfai, B., Balázsfi, D., Hangya, B., Schwarcz, A.D., Szabadits, E., et al. (2022). Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions. J. Exp. Med. 219.

Cserép, C., Pósfai, B., Lénárt, N., Fekete, R., László, Z.I., Lele, Z., Orsolits, B., Molnár, G., Heindl, S., Schwarcz, A.D., et al. (2020). Microglia monitor and protect neuronal function through specialized somatic purinergic junctions. Science (80-. ). 367.

Cserép, C., Schwarcz, A.D., Pósfai, B., László, Z.I., Kellermayer, A., Környei, Z., Kisfali, M., Nyerges, M., Lele, Z., Katona, I., et al. (2022). Microglial control of neuronal development via somatic purinergic junctions. Cell Rep. 40, 111369.

Szalay, G., Martinecz, B., Lénárt, N., Környei, Z., Orsolits, B., Judák, L., Császár, E., Fekete, R., West, B.L., Katona, G., et al. (2016). Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke. Nat. Commun. 7, 11499.