Glial Regulated Neuronal Plasticity
Our research aims to discover new glial-based mechanisms of information processing in the brain in health and disease, with a focus on the role of astrocytes in the regulation of myelin and synaptic plasticity.
Glial cells have traditionally been viewed to support neuronal functions, however, research of the last 2 decades suggests that glial cells may do more than just supporting neuronal function. Our research aims to contribute to a better understanding of the role of glial cells in the regulation of neuronal plasticity in health and disease. For this purpose, we focus on the role of astrocytes in myelination and synapse function. Experiments are being performed both in vitro (e.g. neuron-glial cell cocultures) and in vivo (e.g. molecular analysis and genetic manipulation of astrocytes)
Research line: Astrocyte-synapse interactions in learning and memory
In recent years an intriguing representation of the synapse has emerged in which astrocytes and neuronal synaptic elements function together as active partners in the modulation of synaptic transmission. This new view promises to advance our understanding and to deliver treatments of human brain disorders. We therefore aim to address the role of perisynaptic astrocyte molecules in learning and memory, and to translate our findings on the diseased tripartite synapse in preclinical disease models, e.g. Alzheimer Disease, mild cognitive impairment, (MCI) and post-traumatic stress disorders (PTSD).
Research line: Lipids in neuron-glia interactions
Lipid metabolic disorders often produce neurological defects associated with defects in myelination or synapse development. We recently identified SREBP transcription factors as important regulators of glial lipid synthesis. Current research aims to understand how expression and secretion of astrocyte lipids is implicated in neuronal development and function, and to which extent lipid dietary interventions are successful for treatment of neurological disorders associated with lipid metabolic defects.
Camargo N, Goudriaan A, van Deijk AF, Otte WM, Brouwers JF, Lodder H, Gutmann DH, Nave KA, Dijkhuizen RM, Mansvelder HD, Chrast R, Smit AB, Verheijen MHG. Oligodendroglial myelination requires astrocyte-derived lipids. PLoS Biol. 2017; 26;15(5):e1002605
van Deijk AF, Camargo N, Timmerman J, Heistek T, Brouwers JF, Mogavero F, Mansvelder HD, Smit AB, Verheijen MH. 2017. Astrocyte lipid metabolism is critical for synapse development and function in vivo. Glia. 2017; 65(4):670-682
Goudriaan A, de Leeuw C, Ripke S, Hultman CM, Sklar P, Sullivan PF, Smit AB, Posthuma D, Verheijen MH. Specific glial functions contribute to schizophrenia susceptibility. Schizophr Bull. 2014; 40(4):925-35.
Chrast, R., Saher, G., Nave, K.A., and Verheijen, M.H. Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models. Journal of lipid research, 2011; 52(3): 419-434.
Verheijen, M.H., Camargo, N., Verdier, V., Nadra, K., de Preux Charles, A.S., Medard, J.J., Luoma, A., Crowther, M., Inouye, H., Shimano, H., Chen, S., Brouwers, J.F., Helms, J.B., Feltri, M.L., Wrabetz, L., Kirschner, D., Chrast, R., and Smit, A.B. SCAP is required for timely and proper myelin membrane synthesis. Proceedings of the National Academy of Sciences of the United States of America 2009; 106(50): 21383-21388.
Verheijen, M.H., Chrast, R., Burrola, P., and Lemke, G. Local regulation of fat metabolism in peripheral nerves. Genes Dev 2003; 17(19): 2450-2464.