Glial Regulated Neuronal Plasticity

Research Focus
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.

Key publications

Kotah JM, Kater MSJ, Brosens N, Lesuis SL, Tandari R, Blok TM, Marchetto L, Yusaf E, Koopmans FTW, Smit AB, Lucassen PJ, Krugers HJ, Verheijen MHG, Korosi A. Early-life stress and amyloidosis in mice share pathogenic pathways involving synaptic mitochondria and lipid metabolism. Alzheimers Dement. 2023 Dec 6. doi: 10.1002/alz.13569

Aina Badia-Soteras, Tim S. Heistek, Mandy S.J. Kater, Aline Mak, Adrian Negrean, Michel C. van den Oever, Huibert D. Mansvelder, Baljit S. Khakh, Rogier Min, August B. Smit, Mark H.G. Verheijen. Retraction of astrocyte leaflets from the synapse enhances fear memory. Biological Psychiatry (2022) https://doi.org/10.1016/j.biopsych.2022.10.013

Kater MSJ, Huffels CFM, Oshima T, Renckens NS, Middeldorp J, Boddeke EWGM, Smit AB, Eggen BJL, Hol EM, Verheijen MHG. Prevention of microgliosis halts early memory loss in a mouse model of Alzheimer’s disease. Brain Behav Immun. 2022 Oct 18;107:225-241.

Sapkota D, Kater MSJ, Sakers K, Nygaard KR, Liu Y, Koester SK, Fass SB, Lake AM, Khazanchi R, Khankan RR, Krawczyk MC, Smit AB, Maloney SE, Verheijen MHG, Zhang Y, Dougherty JD. Activity-dependent translation dynamically alters the proteome of the perisynaptic astrocyte process. Cell Rep. 2022 Oct 18;41(3):111474. doi: 10.1016/j.celrep.2022.111474.

Goudriaan A, Loos M, Spijker S, Smit AB, Verheijen MHG. Genetic Variation in CNS Myelination and Functional Brain Connectivity in Recombinant Inbred Mice. Cells. 2020 Sep 18;9(9):2119.

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