Matteo Bergami - C 03

Accruing evidence indicates that glial cells play pivotal roles in maintaining multiple forms of metabolic coupling with neurons and the brain microvasculature. In particular, astrocytic end-feet functionally ensheathe most of the vascular network and serve as specialized exchange sites for ions and energy substrates with brain parenchyma. While in physiological conditions these functions contribute to neurovascular coupling, the precise sub-cellular changes occurring at the glio-vascular interface during brain injury are much less understood.

We have recently shown an important role for mitochondrial network dynamics in perivascular astrocytic end-feet during injury, and how altering these dynamics impacts vascular remodeling. A major focus of this funding period will therefore be that of investigating specific signalling pathways linked to mitochondrial dynamics in perivascular astrocytes. The expected results will disclose the relevance of astroglial metabolism in sustaining brain tissue remodelling and how glial cell manipulation may facilitate tissue repair.

1. Assessing the role of specific mitochondrial-derived signaling pathways in reactive astrocytes 

2. Characterization of mitochondrial metabolism in reactive astrocytes 

1. Göbel J, Pelzer P, Engelhardt E, Sakthivelu V, Jahn HM, Jevtic M, Folz-Donahue K, Kukat C, Schauss A, Frese CK, Ghanem A, Conzelmann KK, Motori E, Bergami M. Mitochondrial fusion in reactive astrocytes coordinates local metabolic domains to promote vascular repair. BioRxiv (2019); doi:https://doi.org/10.1101/657999.
2. Göbel J, Motori E, Bergami M. Spatiotemporal control of mitochondrial network dynamics in astroglial cells. Biochem Biophys Res Commun(2018); 500:17-25.
3. Motori, E.^#, Puyal, J., Toni, N., Ghanem, A., Angeloni, C., Malaguti, M., Cantelli-Forti, G., Berninger, B., Conzelmann, K.K., Götz, M., Winklhofer, K., Hrelia, S.*, and Bergami, M.*^,# Inflammation-induced alteration of astrocyte mitochondrial dynamics requires autophagy for mitochondrial network maintenance. Cell Metab (2013); 18, 844-859. ^#co-corresponding; *equal contribution.