Comparison of three human microglia models to study schizophrenia Paul R. Ormel1,2, Renata Vieira de Sá1, R. Jeroen Pasterkamp1, René S. Kahn2,3, Elly M. Hol1, Lot D. de Witte1,2,3 1Department of Translational Neuroscience, 2Department of Psychiatry, Brain Center Rudolf Magnus, UMC Utrecht, Utrecht, The Netherlands; 3Department of Psychiatry, Icahn Medical School, Mount Sinai, New York, NY, United States of America
Schizophrenia (SCZ) is a psychiatric disease and new insights reveal that the immune system is involved in the pathogenesis. SNPs in immune-related genes, co-occurrence of immune-related disorders, and elevated inflammatory markers in brain, CSF, and plasma are all linked to SCZ. Microglia are the main immune cells of the central nervous system and shape neuronal architecture by inducing synaptogenesis and mediating synaptic refinement, both processes which are thought to be affected in SCZ. Recently, several methods have been developed to study human microglia, but which of these methods would be best to study the role of microglia in SCZ? We have compared three methods: acute isolation of microglia from post mortem human brain tissue, generation of microglia from patient-derived monocytes, and iPSC-derived microglia models. Transcriptomic and functional data show that these methods all result in microglia(-like) cells, which have their own specific benefits or pitfalls that should be taken into account when choosing a model. Things to consider are: duration experiments, costs, availability of patient(s) (material), possibilities for co-culture systems. Although the iPSC models open up a lot of new possibilities, these cells will not fully replace post mortem microglia or monocyte-derived microglia models.
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