Neurosciences - Posters H
Eszter Császár1, Nikolett Lénárt1, Csaba Cserép1, Zsuzsanna Környei1, Balázs Pósfai1, Diána Balázsfi1, Anett Schwarcz1 and Ádám Dénes1
1 Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest
Introduction: Microglia, the main resident immune cells of the brain parenchyma are key regulators of inflammatory processes in the central nervous system. Despite the broad implication of microglial actions in shaping neuronal function in health and disease, their role in cerebral blood flow (CBF) remained vaguely defined.
Aims: The aim of the study was to investigate the mechanisms of microglia-vascular interactions in order to understand the possible role of microglial actions on cerebral blood flow modulation.
Method: Formation of contacts between microglia and other cell types in the neurovascular unit was assessed by in vivo two-photon imaging and high resolution anatomy (confocal microscopy, immunoelectron microscopy and electron tomography), using the microglia-specific marker, P2Y12 receptor. CBF changes in the circulation were measured by Functional Ultrasound and Laser Speckle Contrast Imaging through the intact skull bone. The role of microglial actions were investigated via elimination of microglia by PLX5622, by using P2Y12R-/- mice, or blocking P2Y12R signalling in microglia by PSB-0739 injected into the cisterna magna. Whisker stimulation or visual stimulation was used to investigate neurovascular coupling in the barrel or in the visual cortex, respectively.
Results: Our anatomical data show that microglia dynamically contact different levels of the vascular tree in vivo and form direct purinergic contacts with the cells of the neurovascular unit in both the mouse and the human brain, which shape CBF. We found that through these interactions microglia modulate CBF, via purinergic actions during neurovascular coupling, hypercapnia-induced vasodilation and adaptation to hypoperfusion.
Conclusion: Our data also show that microglia may be able to sense different perfusion-related changes in the NVU and interact with different cell types in a compartment-specific manner. Our findings demonstrate that microglia should be considered as an important modulatory cell type involved in physiological and pathological alterations of CBF and understanding their actions may facilitate the discovery of novel treatment opportunities in common neurological disorders.
Funding: ERC-CoG 724994 (Á.D.), the “Momentum” Program of HAS (LP2022-5/2022 to Á.D.) and ÚNKP-22-4-I-SE-1 (E.Cs.) the New National Excellence Program of the Ministry for Innovation and Technology.