The selective serotonin reuptake inhibitor, fluoxetine (FLX), is widely used to treat depression and anxiety disorders. Previous studies have demonstrated that FLX treatment can reverse the established neuronal maturation of granule cells in the hippocampal dentate gyrus, and of inhibitory interneurons in the basolateral amygdala. FLX can also increase hippocampal adult neurogenesis, which is the most widely reported effect. Recently, using immunohistological methods, we found that chronic FLX treatment decreased the levels of parvalbumin, which could be used as a maturation marker of fast-spiking interneurons, and perineuronal nets (PNNs), which are formed mainly around mature fast-spiking interneurons, in the medial frontal cortex (mFC) of adult mice, suggesting that FLX induces pseudo-immature status of these types of neurons. In this study, to further characterize the effect of FLX on mFC, we compared genome-wide gene expressions of FLX-treated mFC with those of the corresponding region of normally developing brains in mice. We found that the mFC in adult mice treated with FLX resembled juvenile mFC in terms of genome-wide expression profile. The common gene alterations between FLX-treated mFC of adult mice and mFC of normally developing mice might be partly accounted for by maturational abnormalities in fast-spiking interneurons, astrocytes, and oligodendrocytes, although the contributions of other cell types to the transcriptomic immaturity of the mFC treated with FLX cannot be excluded. In addition, gene expression patterns in the FLX-treated mFC of adult mice were similar to those in the developing mFC of humans. Our results suggest that FLX treatment induces pseudo-immaturity of the mFC of adult mice with respect to gene expression patterns.
This work was supported by CREST and NEXT Program.