Melatonin modifies SOX2⁺cell proliferation in dentate gyrus and modulates SIRT1 and MECP2 in long-term sleep deprivation

Abstract

Melatonin is a pleiotropic molecule that, after a short-term sleep deprivation, promotes the proliferation of neural stem cells in the adult hippocampus. However, this effect has not been observed in long-term sleep deprivation. The precise mechanism exerted by melatonin on the modulation of neural stem cells is not entirely elucidated, but evidence indicates that epigenetic regulators may be involved in this process. In this study, we investigated the effect of melatonin treatment during a 96-hour sleep deprivation and analyzed the expression of epigenetic modulators predicted by computational text mining and keyword clusterization. Our results showed that the administration of melatonin under sleep-deprived conditions increased the MECP2 expression and reduced the SIRT1 expression in the dentate gyrus. We observed that let-7b, mir-132, and mir-124 were highly expressed in the dentate gyrus after melatonin administration, but they were not modified by sleep deprivation. In addition, we found more Sox2 + /5-bromo-2′-deoxyuridine (BrdU) + cells in the subgranular zone of the sleep-deprived group treated with melatonin than in the untreated group. These findings may support the notion that melatonin modifies the expression of epigenetic mediators that, in turn, regulate the proliferation of neural progenitor cells in the adult dentate gyrus under long-term sleep-deprived conditions. All procedures performed in this study were approved by the Animal Ethics Committee of the University of Guadalajara, Mexico (approval No. CI-16610) on January 2, 2016.

Melatonin-induced suppression of DNA methylation promotes odontogenic differentiation in human dental pulp cells

“…On the other hand, Tao et al [ 47 ] have reported that MeCP2 knockdown led to downregulation of vascular smooth muscle cell proliferation. Besides, similar change that MT increased the MeCP2 expression during proliferation occurred in neural stem cells in the adult hippocampus under sleep-deprived conditions [ 48 ]. Therefore, we suggest that MeCP2 plays an essential role in DNA methylation in hDPCs.…”

Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure

“…One of the roles that this protein plays in the brain is to maintain the identity of the neural precursors [ 77 , 78 ], and therefore, it is considered a marker of neural progenitors and stem cells [ 79 ]. Numerous investigations have demonstrated its participation in the neurogenic process [ 80 ]; elevated levels of the Sox2 protein have been reported in patients undergoing treatment for the depressive state [ 81 ]. We were able to find that our model generated a lack of this protein, whereas the inhibition of FAAH was able to restore the levels of this molecule unless antagonism of CB1R was provoked.…”

Progress in studies of epidermal stem cells and their application in skin tissue engineering

“…The most commonly used DNA-label method is the BrdU pulse-chase method. The dividing cells can be marked and their division history can be followed by using this method [47]. As a pyrimidine analog of thymidine, BrdU can incorporate into DNA during DNA synthesis process.…”