A thioredoxin-Serinc2-lipid signaling axis modulates mood-related behaviors in mice [ATAC-Seq]

However, the molecular basis underlying subtype-specific features remains poorly understood. Here, we showed that Serinc2, a BD susceptibility gene encoding a L-serine transporter that regulates membrane lipid synthesis, as a regulator of mood-related behavioral phenotypes.

Using patient plasma samples, BD iPSC-derived forebrain organoids, and Serinc2 knockout/overexpression mouse models, we found that Serinc2 expression was increased in bipolar I (BDI) but decreased in bipolar II (BDII); bi-directional manipulation of Serinc2 induced opposite changes in synaptic transmission and depression-related behaviors, accomplied by alterations in PS/SM-dependent redistribution of NMDAR subunits in postsynaptic membranes.