Rapamycin increases the incidence of neuropsychiatric illness in kidney transplant patients through the suppression of neural stem cells.
Yangsik KimJung Sun LeeYeon Ho JooPublished in: Translational psychiatry (2020)
Rapamycin inhibits protein translation in cells, including neural stem cells (NSCs), by suppressing the mechanistic target of rapamycin (mTOR). This drug has been widely used together with calcineurin inhibitors in transplantation patients to prevent graft rejection. Previous studies have reported an association between mTOR and depression, but few investigations of this have occurred in transplant recipients. We have here tested the psychiatric effects of rapamycin in mice. The animals treated with rapamycin showed decreased locomotion and sugar consumption. In these rapamycin-treated mice also, the granule cells in the dentate gyrus (DG), which actively differentiate and proliferate from NSC, showed decreases in both excitatory and inhibitory synaptic transmission. Furthermore, the SOX2/NeuN ratio in the DG was decreased in mice treated with rapamycin. We further show that kidney transplantation patients who are receiving rapamycin have more psychiatric disorder such as adjustment disorder. Clinical attention is thus needed when administering rapamycin to transplant recipients due to its behavioral effects and its impact on NSC.
Keyphrases
- end stage renal disease
- newly diagnosed
- chronic kidney disease
- ejection fraction
- neural stem cells
- prognostic factors
- peritoneal dialysis
- induced apoptosis
- kidney transplantation
- stem cells
- transcription factor
- mental health
- oxidative stress
- cell proliferation
- depressive symptoms
- working memory
- adipose tissue
- type diabetes
- cell cycle arrest
- patient reported
- patient reported outcomes
- cell death
- mesenchymal stem cells
- signaling pathway
- small molecule
- electronic health record
- protein protein