Journal of Pineal Research最新文献

The glymphatic system is a critical waste clearance system in the brain, playing an essential role in maintaining homeostasis within the central nervous system. Aquaporin 4 (AQP4), an indispensable component of the glymphatic system, is vital for ensuring the proper function of this system. Melatonin has been proven to be protective in treating hypoxic-ischemic encephalopathy (HIE). The aim of this study was to examine if alterations occur in the glymphatic system function in the brain of HIE model rats, and to determine whether melatonin can enhance the function of the glymphatic system by regulating AQP4, along with elucidating the mechanisms underlying melatonin's effects on AQP4. 10-day-old rat pups were subjected to hypoxic-ischemic (HI) injury; melatonin and roscovitine (an inhibitor of cyclin-dependent kinase 5) were injected intraperitoneally at 10 min following HI induction. At 24 h post-HI, intracisternal tracer infusion, neurobehavioral tests, immunofluorescence staining, western blot analysis, Evans blue (EB) permeability assay, brain water content test, ELISA detection, and co-immunoprecipitation tests were performed. At 28 days post-HI, neurobehavioral tests, intracisternal EB infusion, Nissl staining, and cerebral blood flow (CBF) evaluations were performed. The results showed that melatonin improved neurological function, restored glymphatic function, maintained blood–brain barrier integrity, alleviated brain edema, increased CBF, and reduced brain atrophy; both melatonin and roscovitine inhibited cyclin-dependent kinase 5 (CDK5) activity, enhanced the interaction between AQP4 and alpha-syntrophin (α-Syn), and maintained AQP4 polarity. In conclusion, the current study suggests that melatonin may enhance the interaction between AQP4 and α-Syn by inhibiting CDK5 activity after HI to maintain glymphatic function.

Melatonin is a known pleiotropic antioxidant and signaling molecule, found in both plants and animals. Although melatonin was found to translocate via the human glucose transporter 1 (GLUT1), any mechanism of transporter-mediated uptake of melatonin has remained unknown in plants. In the present manuscript, we found an orthologue of GLUT1 in tobacco and established its role as a functional phytomelatonin transporter (MelT) using fluorescence tracking, via melatonin-conjugated quantum dot nanoparticles. Overexpression of NtMelT in the model plant Nicotiana benthamiana showed increased uptake of the conjugated nanofluorophores to a maximum of 5.4-fold in roots and 2.1-fold in leaves, while application of N-ethylmaleimide (inhibitor of glucose transporter) suppressed their translocation. This ensured the specificity of NtMelT for transporting melatonin. Due to increased uptake and distribution, the transgenic lines maintained a maximum of 4.6-fold more endogenous melatonin. The transgenics were tolerant against arsenic, copper, lead, nickel, and fluoride toxicity. Increased activity of the enzymatic antioxidants detoxified excess reactive oxygen species and alleviated the associated physiological injuries. Translocation of melatonin significantly reduced bioaccumulation of the toxic pollutants and ensured normal flowering and seed setting in the transgenic plants. Overall, the present research provides a solution for safe rice cultivation under polluted environment.

The pineal secretion of the hormone melatonin demonstrates a circadian (~24 h) rhythm with the onset of melatonin production at night and offset each morning under tight circadian control for entrained individuals. Melatonin exerts both acute sleep-promoting effects and phase-shifting effects on the circadian clock. Due to its hypnotic and chronobiotic (phase shifting) effects, exogenous melatonin supplements are increasingly being used as a treatment for a variety of sleep and circadian diseases and disorders. Phase shifting of the circadian clock can also be accomplished through ocular exposure to light. However, the interacting effects of light and melatonin on the circadian clock are not well understood. To analyze the dynamic behavior of both endogenous and exogenous melatonin's influence on the circadian clock, we extend a previously published mathematical model of the circadian clock to account for forcing due to both endogenous melatonin produced by the pineal gland and exogenous melatonin entering the system through ingested oral supplements. We fit model parameters using published melatonin pharmacokinetics, a melatonin suppression illuminance-response curve, and a 3-pulse 3 mg melatonin phase response curve (PRC). Simulated microscopic PRCs to light and melatonin are determined by the model fits and demonstrate a relative phase difference consistent with previous observations in experimental PRC data. Finally, we simulate a phase advancing experimental protocol utilizing both light exposure and exogenous melatonin to generate model predictions for the effects of interacting inputs to the clock. This modeling framework allows for the study of melatonin's dynamic properties and interaction with the circadian clock. Furthermore, it provides a framework for determining optimal light exposure and exogenous melatonin administration schedules to induce desired phase shifting of the circadian clock.

In climacteric fruits like banana (Musa spp.), ripening is driven by ethylene production and increased respiration, leading to rapid softening, quality loss, and disease susceptibility. This study was aimed to evaluate the effect of postharvest melatonin dip (1.0 mM and 1.5 mM for 15 min) on Red Banana stored under ambient and cold storage conditions. Melatonin significantly suppressed ethylene biosynthesis (Cohen's d ƞ² = 0.85), reduced respiration rate (ƞ² = 0.89), and delayed textural degradation by inhibiting cell wall-degrading enzymes (polygalacturonase, pectin methyl esterase, amylase, cellulase, and β-glucosidase) with 35.94% and 45.48% reduction in cumulative enzyme activity under ambient and cold storage, respectively. It also enhanced antioxidant enzyme activity resulting in 1.8- and 1.5-fold increases in enzyme activity in ambient and cold storage, respectively, mitigating oxidative stress and reducing anthracnose incidence. Consequently, melatonin extended shelf life by 2.67 days in ambient storage and 5.33 days in cold storage, without inducing chilling injury. These findings highlight melatonin as a natural, eco-friendly alternative, offering a sustainable strategy to enhance Red Banana storage and reduce postharvest losses. Its ability to modulate fruit metabolism, enhance stress responses, and membrane protection properties underscores its applied potential in postharvest management.

Human dental pulp stem cells (hDPSCs) exhibit amazing therapeutic abilities in a variety of diseases due to their remarkable self-renewal capacity and multi-differentiation potential. However, their therapeutic potential could be weakened by various factors such as oxidative stress in cell survival microenvironment In Vivo. Here, we explored the protective effect and mechanism of melatonin (Mel) on hDPSCs transplanted in a type 1 diabetes mellitus (T1DM) rat model. Nicotinamide adenine dinucleotide (NAD⁺) metabolism and mitochondrial function were remarkably impaired in T1DM rats caused by oxidative stress, while the combination of Mel and post-hDPSCs transplantation could rebalance NAD⁺ homeostasis through regulating NAMPT-NAD⁺-SIRT1 axis. Furthermore, Mel significantly reduced intracellular and mitochondrial reactive oxygen species, and alleviated cell senescence and apoptosis of hDPSCs exposed to hydrogen peroxide through ameliorating NAD⁺ depletion and mitochondrial dysfunction. The protective role of Mel could be extremely essential to stem cells in tissue engineering and regenerative medicine.

Light and temperature change constantly under natural conditions and play vital roles in coordinating plant morphogenesis. However, how these two signals are integrated with endogenous signals to fine-tune plant morphology requires further investigation. Given that phytomelatonin is a multifunctional regulator connecting environmental signals and plant development, here we propose that phytomelatonin is involved in the integration of light and temperature signals. When co-treated with darkness and warm ambient temperature, the light–temperature signal showed synergistic upregulation of phytomelatonin synthesis and thus hypocotyl growth. Phytomelatonin synthesis gene SEROTONIN N-ACETYLTRANSFERASE (SNAT) was induced under constant darkness or warm temperature, reaching its peak level under the combined treatment. The snat mutant, with reduced phytomelatonin content and hypocotyl length, was less sensitive to darkness and warm temperature, whereas 35S::SNAT-GFP had more phytomelatonin and longer hypocotyls than the wild type, indicating that SNAT is needed for light–temperature morphogenesis. Furthermore, SNAT expression and phytomelatonin content were reduced in cop1 but increased in hy5. HY5 inhibits SNAT expression by binding to its promoter. The hy5 snat seedlings had less phytomelatonin and shorter hypocotyls than the hy5 seedlings, along with the SNAT mutation in 35S::COP1 snat seedlings reversed the phenotype of 35S::COP1, further verifying that SNAT acts downstream of COP1-HY5 module. Moreover, RNA-Seq revealed that phytomelatonin is associated with light–temperature signal in controlling hypocotyl elongation-related genes. Taken together, our results showed that the light–temperature signal regulates SNAT-mediated phytomelatonin synthesis through COP1-HY5 module to coordinate plant morphogenesis.