TRIP6 promotes neural stem cell maintenance through YAP-mediated Sonic Hedgehog activation.

In the adult mammalian brain, new neurons are continuously generated from neural stem cells (NSCs) in the subventricular zone (SVZ)-olfactory bulb (OB) pathway. YAP, a transcriptional co-activator of the Hippo pathway, promotes cell proliferation and inhibits differentiation in embryonic neural progenitors. However, the role of YAP in postnatal NSCs remains unclear. Here, we showed that YAP was present in NSCs of the postnatal mouse SVZ. Forced expression of Yap promoted NSC maintenance and inhibited differentiation, whereas depletion of Yap by RNA interference or conditional knockout led to the decline of NSC maintenance, premature neuronal differentiation, and collapse of neurogenesis. For the molecular mechanism, thyroid hormone receptor-interacting protein 6 (TRIP6) recruited protein phosphatase PP1A to dephosphorylate LATS1/2, therefore inducing YAP nuclear localization and activation. Moreover, TRIP6 promoted NSC maintenance, cell proliferation, and inhibited differentiation through YAP. In addition, YAP regulated the expression of the Sonic Hedgehog (SHH) pathway effector Gli2 and Gli1/2 mediated the effect of YAP on NSC maintenance. Together, our findings demonstrate a novel TRIP6-YAP-SHH axis, which is critical for regulating postnatal neurogenesis in the SVZ-OB pathway.

Predictors of adherence to an antidepressant medication regimen among patients diagnosed with depression in Taiwan.

This study explored the predictors of medication adherence among Taiwanese people with major depression and dysthymic disorder. Previous research indicates that depressed patients vary in compliance with their medication regimen. Poor compliance reduces the therapeutic effect of medication. Self-report questionnaires were used for this cross-sectional study conducted with 181 outpatients diagnosed with major depression or dysthymic disorder. About 50% of depressed patients reported good medication adherence. The predictors of adherence were patient income, treatment efficacy, and understanding the importance of continuing medication. Professionals should use collaborative communication and cultural values clarification with depressed patients and their families to improve the awareness of illness and to increase the likelihood of medication compliance.