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Bipolar disorder is a severe chronic psychiatric disorder affecting 1% of the population. Lithium is its gold standard treatment. Human MRI and preclinical studies suggest that it may increase neurogenesis, neuroprotection, myelination and modulate synaptic plasticity and neuroinflammation. However, many aspects of its mode of action remain unknown: which cellular effects are associated with the “MRI effects” of lithium in patients? Are its therapeutic cellular effects region specific or brain wide? We will conduct 2 parallel studies (in rats and humans) using similar (longitudinal) designs and methods ([11C]-UCB-J PET and MRI) plus histology and immunochemistry in the rats. We will assess synaptic plasticity, myelination, oligodendrocytes, neurogenesis and neuroinflammatory aspects associated with lithium in the same study. We will thus be able to draw inferences and inter species correspondences between PET/MR findings and immunohistological findings
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