PhD Scientific Days 2021

NE_II_L: Neurosciences II. Lectures

Molecular Anatomy and Function of Somatic Microglia-Neuron Junctions

Text of the abstract

Introduction: Understanding the mechanisms of neurological diseases is one of the most urgent challenges of medicine. To date the majority of studies focused solely on neurons, however, to get an insight into neurodegenerative processes we have to examine all the celltypes and their complex interplay in the central nervous system.
Aim: Recently we identified a new type of communicational interface between microglial processes and neuronal cell bodies, through which microglia are able to monitor and modify neuronal activity. Our aim is to uncover the ultrastructure of these somatic junctions and explore their function in human pathologies.
Methods: We explored multiple immunofluorescent-labeled brain samples with confocal laser scanning microscopy and stimulated emission depletion (STED) microscopy. We examined the somatic junction-related subcellular localization of a broad range of proteins that could have a putative role in microglia-neuron communication.
Results: In the physiological mouse brain we identified the complement protein C1q as an internal protein of somatic junctions - a macromolecule that is essential for developmental synaptic pruning executed by microglia. We also frequently observed the gap junction-forming GJA3 protein on the microglial side of junctions. Oppositely of formerly identified elements of somatic junctions, these proteins are not present at every interaction site, which suggests functional heterogeneity among these contacts.
Conclusion: We are currently exploring further potential elements (e.g. SigmaR, Cx-43) of somatic junctions, as well as changes in expression of C1q and GJA3 in pathologies. Furthermore, we are also focusing on the localization and potential alteration of all identified components of somatic junctions on healthy and pathologic human samples. Our results provide insight into complex molecular processes that could open up new and targeted therapeutic approaches in human neuropathologies.
Funding: This work was supported by the New National Excellence Program of the Ministry for Innovation and Technology (ÚNKP-20-3-II to BP, ÚNKP-20-5 to CC) and by the Doctoral School of Semmelweis University (Semmelweis 250+ Kiválósági PhD Ösztöndíj, EFOP-3.6.3-VEKOP-16-2017-00009, Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése).

University and Doctoral School

Semmelweis University, János Szentágothai Doctoral School of Neurosciences