Marta Mota
The etiology of major depressive disorder (MDD) remains poorly understood, but one leading hypothesis implicates neuroinflammation in its pathophysiology. Once viewed as a liver-derived peripheral system, complement is now recognized to be locally produced by neurons and glial cells and to bridges the innate immune system with synaptic plasticity and neurodevelopment/neurodegeneration. Previous clinical studies have reported elevated levels of complement proteins in the serum of individuals with MDD compared to healthy controls.
My PhD project is part of a multidisciplinary iCNS team investigating the complement system, from protein structure to functional cascade analyses under both homeostatic and disease conditions. We aim to characterize complement expression and its relationship with neuroglial cells in a cohort of MDD patients obtained from the Netherlands Brain Bank–Psychiatry. In addition, we will use available antibodies targeting complement proteins and develop nanobodies and activity-based probes to visualize activated protein forms. These chemical tools will be tested and optimized in a sophisticated platform based on murine cortical organotypic slice cultures, allowing us to manipulate complement pathways under healthy and neuroinflammatory conditions. Live imaging in mice, combined with patch-clamp recordings from pyramidal neurons and interneurons, will be used to examine the spatiotemporal dynamics of the complement system.
By combining these approaches, we expect to gain deeper insight into the mechanistic role and therapeutic potential of complement in MDD.