Browsing by Author "Murillo-Rodríguez, Eric"
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- An overview of the clinical uses, pharmacology, and safety of modafinilPublication . Murillo-Rodríguez, Eric; Veras, André Barciela; Rocha, Nuno Barbosa; Budde, Henning; Machado, Sérgio; Rocha, NunoModafinil (MOD) is a wakefulness-inducing compound prescribed for treatment of excessive daytime sleepiness as a consequence of sleep disturbances such as shift work sleep disorder, obstructive sleep apnea, restless leg syndrome, or narcolepsy. While providing effective results in patients with sleepiness, MOD also produces positive outcomes in the management of fatigue associated with different conditions including depression, cancer, or tiredness in military personnel. Although there is clear evidence of the stimulant effects of MOD, current data also show that administration of this drug apparently induces positive neurobiological effects, such as improvement in memory. However, serious concerns have been raised since some reports have suggested MOD dependence. Taken together, these findings highlight the need to characterize the changes induced by MOD which have been observed in several neurobiological functions. Moreover, further work should follow up on the likely long-term effects of this drug if used for treatment of drowsiness and tiredness. Here, we review and summarize recent findings of the medical uses of MOD in the management of sleepiness and fatigue associated with depression or cancer as well as exhaustion in military personnel. We also discuss the available literature related with the cognitive enhancing properties of this stimulant, as well as what is known and unknown about MOD addiction.
- Assessing the management of excessive daytime sleepiness by napping benefitsPublication . Murillo-Rodríguez, Eric; Yamamoto, Tetsuya; Monteiro, Diogo; Budde, Henning; Rocha, Nuno; Cid, Luis; Teixeira, Diogo S.; Telles-Correia, Diogo; Veras, André Barciela; Machado, Sérgio; Imperatori, Claudio; Torterolo, PabloPurpose Demanding lifestyle characterized by extended working hours, shift work schedules as well as excessive use of mobile gadgets leads to the disruption of the circadian and homeostatic factors affecting the sleep quality of individuals. As consequence, subjects complain of suffering several sleep disorders some of them characterized by inducing excessive daytime sleepiness (EDS). Currently, the therapeutic approaches for managing EDS include medication, promotion of sleep hygiene, cognitive and behavioral therapy or using of continuous positive airway pressure machine. In this review, we propose the posology of the personalized sleep medicine by the prescription of naps for treating EDS. Methods This review included the online search in PubMed and manual review of articles (basic and clinical trials) of a range of personalized medicine potentially associated to factors of dosage in areas such as nutrition, sports and sleep. Articles in English were identified and subsequently analyzed for consideration for this review. Results Current evidence has demonstrated that naps exert positive outcomes for individuals complaining with EDS. The dosage of naps might follow similar procedures as reported for personalized interventions in diets or exercise programs (by taking the right dose, at the proper time, with a recommended frequency) which have demonstrated successfully results. Conclusions The management of EDS may include the personalized sleep medicine considering the prescription of dosage of naps.
- CRISPR/Cas9, the Powerful New Genome-Editing Tool for Putative Therapeutics in ObesityPublication . Franco-Tormo, María José; Salas-Crisostomo, Mireille; Rocha, Nuno; Budde, Henning; Machado, Sérgio; Murillo-Rodríguez, EricThe molecular technology known as clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) is revolutionizing the field of medical research and deepening our understanding of numerous biological processes. The attraction of CRISPR/Cas9 lies in its ability to efficiently edit DNA or modulate gene expression in living eukaryotic cells and organisms, a technology that was once considered either too expensive or scientifically risky. CRISPR/Cas9 has been successfully applied in agriculture to develop the next generation of disease-resistant plants. Now, the capability of gene editing has been translated to the biomedical area, focusing on the future of medicine faced with drug-resistant microbes by selectively targeting genes involved in antibiotic resistance, for example, or finding the ultimate strategy for cancer or HIV. In this regard, it was recently demonstrated that an injection of cancer-fighting CRISPR-modified white blood cells in a patient suffering from metastatic lung cancer could lead to promising results. Researchers and bioethicists are debating questions about the regulation of CRISPR/Cas9 that must be addressed. While legal challenges surround the use of this technique for genetically modifying cell lines in humans, we review the basic understanding of CRISPR/Cas9 and discuss how this technology could represent a candidate for treatment of non-communicable diseases in nutrition, such as obesity.
- Detrimental role of prolonged sleep deprivation on adult neurogenesisPublication . Fernandes, Carina; Rocha, Nuno; Rocha, Susana; Herrera-Solís, Andrea; Salas-Pacheco, José; García-García, Fabio; Murillo-Rodríguez, Eric; Yuan, Ti-Fei; Machado, Sergio; Arias-Carrión, OscarAdult mammalian brains continuously generate new neurons, a phenomenon called adult neurogenesis. Both environmental stimuli and endogenous factors are important regulators of adult neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and adult neurogenesis in brain function, such as learning, memory, and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on adult neurogenesis.
- Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasisPublication . Murillo-Rodríguez, Eric; Machado, Sergio; Rocha, Nuno; Budde, Henning; Yuan, Ti-Fei; Arias-Carrión, OscarThe endocannabinoid system comprises receptors (CB1 and CB2 cannabinoid receptors), enzymes (Fatty Acid Amide Hydrolase [FAAH], which synthesizes the endocannabinoid anandamide), as well as the anandamide membrane transporter (AMT). Importantly, previous experiments have demonstrated that the endocannabinoid system modulates multiple neurobiological functions, including sleep. For instance, SR141716A (the CB1 cannabinoid receptor antagonist) as well as URB597 (the FAAH inhibitor) increase waking in rats whereas VDM-11 (the blocker of the AMT) enhances sleep in rodents. However, no further evidence is available regarding the neurobiological role of the endocannabinoid system in the homeostatic control of sleep. Therefore, the aim of the current experiment was to test if SR141716A, URB597 or VDM-11 would modulate the sleep rebound after sleep deprivation. Thus, these compounds were systemically injected (5, 10, 20mg/kg; ip; separately each one) into rats after prolonged waking. We found that SR141716A and URB597 blocked in dose-dependent fashion the sleep rebound whereas animals treated with VDM-11 displayed sleep rebound during the recovery period. Complementary, injection after sleep deprivation of either SR141716A or URB597 enhanced dose-dependently the extracellular levels of dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT), as well as adenosine (AD) while VDM-11 caused a decline in contents of these molecules. These findings suggest that SR141716A or URB597 behave as a potent stimulants since they suppressed the sleep recovery period after prolonged waking. It can be concluded that elements of the endocannabinoid system, such as the CB1 cannabinoid receptor, FAAH and AMT, modulate the sleep homeostasis after prolonged waking.
- Role of N-Arachidonoyl-Serotonin (AA-5-HT) in Sleep-Wake Cycle Architecture, Sleep Homeostasis, and Neurotransmitters RegulationPublication . Murillo-Rodríguez, Eric; Di Marzo, Vincenzo; Machado, Sergio; Rocha, Nuno; Veras, André B.; Neto, Geraldo A. M.; Budde, Henning; Arias-Carrión, Oscar; Arankowsky-Sandoval, GloriaThe endocannabinoid system comprises several molecular entities such as endogenous ligands [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)], receptors (CB1 and CB2), enzymes such as [fatty acid amide hydrolase (FAHH) and monoacylglycerol lipase (MAGL)], as well as the anandamide membrane transporter. Although the role of this complex neurobiological system in the sleep-wake cycle modulation has been studied, the contribution of the blocker of FAAH/transient receptor potential cation channel subfamily V member 1 (TRPV1), N-arachidonoyl-serotonin (AA-5-HT) in sleep has not been investigated. Thus, in the present study, varying doses of AA-5-HT (5, 10, or 20 mg/Kg, i.p.) injected at the beginning of the lights-on period of rats, caused no statistical changes in sleep patterns. However, similar pharmacological treatment given to animals at the beginning of the dark period decreased wakefulness (W) and increased slow wave sleep (SWS) as well as rapid eye movement sleep (REMS). Power spectra analysis of states of vigilance showed that injection of AA-5-HT during the lights-off period diminished alpha spectrum across alertness in a dose-dependent fashion. In opposition, delta power spectra was enhanced as well as theta spectrum, during SWS and REMS, respectively. Moreover, the highest dose of AA-5-HT decreased wake-related contents of neurotransmitters such as dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT) whereas the levels of adenosine (AD) were enhanced. In addition, the sleep-inducing properties of AA-5-HT were confirmed since this compound blocked the increase in W caused by stimulants such as cannabidiol (CBD) or modafinil (MOD) during the lights-on period. Additionally, administration of AA-5-HT also prevented the enhancement in contents of DA, NE, EP, 5-HT and AD after CBD of MOD injection. Lastly, the role of AA-5-HT in sleep homeostasis was tested in animals that received either CBD or MOD after total sleep deprivation (TSD). The injection of CBD or MOD increased alertness during sleep rebound period after TSD. However, AA-5-HT blocked this effect by allowing animals to display an enhancement in sleep across sleep rebound period. Overall, our findings provide evidence that AA-5-HT is an important modulator of sleep, sleep homeostasis and neurotransmitter contents.
- Sistema endocanabinoide y sus efectos en el SNCPublication . Pastrana-Trejo Carlos, José; Macías-Triana, Lorena; Romero-Cordero, Karen; Daniela Soriano-Nava, Marcia; Morales-Lara, Daniela; Rocha, Nuno; Barciela Veras, André; Henning, Budde; Machado, Sérgio; Murillo-Rodríguez, EricLos canabinoides endógenos o endocanabinoides son un grupo de moléculas producidas por el sistema nervioso central (SNC), las cuales ejercen efectos muy parecidos a los canabinoides exógenos. Entre los endocanabinoides más estudiados, tenemos a los lípidos anandamida (ANA), y el 2-araquidonoilglicerol (2-AG). Estas moléculas forman parte del complejo sistema de endocanabinoides, el cual incluye a proteínas transmembranales denominadas, receptores para cannabinoides CB1 y CB2. Adicionalmente, el sistema de endocanabinoides está integrado por enzimas responsables de la hidrólisis de ANA y 2-AG, tales como la fatty acid amyde hydrolase (FAAH) y monoacylglycerol lipase (MAGL), así como del transportador membranal de anandamida. Múltiples evidencias experimentales y preclínicas, han demostrado que el sistema de endocanabinoides, regula diversos fenómenos neurobiológicos, tales como enfermedades neurodegenerativas, obesidad, aprendizaje y memoria, así como el ciclo sueño-vigilia. El estudio de las propiedades neurobiológicas del sistema de canabinoides endógenos, permitirá en un futuro no muy lejano, considerar a dicho sistema, como parte importante del diseño de terapias dirigidas para la prevención, y control de múltiples patologías, incluidas la enfermedad de Alzheimer, obesidad, o trastornos del sueño.
- Sleep and neurochemical modulation by DZNep and GSK-J1: potential link with histone methylation statusPublication . Murillo-Rodríguez, Eric; Arankowsky-Sandoval, Gloria; Barros, Jorge Aparecido; Rocha, Nuno; Yamamoto, Tetsuya; Machado, Sérgio; Budde, Henning; Telles-Correia, Diogo; Monteiro, Diogo; Cid, Luis; Veras, André BarcielaHistone methylation/demethylation plays an important modulatory role in chromatin restructuring, RNA transcription and is essential for controlling a plethora of biological processes. Due to many human diseases have been related to histone methylation/demethylation, several compounds such as 3-deazaneplanocin A (DZNep) or 3-((6-(4,5-Dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoic acid; N-[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-4-pyrimidinyl]-β-Alanine (GSK-J1), have been designed to inhibit histone methylase or suppress histone demethylase, respectively. In the present study, we investigated the effects on the sleep-wake cycle and sleep-related neurochemical levels after systemic injections of DZNep or GSK-J1 given during the light or dark phase in rats. DZNep dose-dependently (0.1, 1.0, or 10 mg/kg, i.p.) prolonged wakefulness (W) duration while decreased slow wave sleep (SWS) and rapid eye movement sleep (REMS) time spent during the lights-on period with no changes observed in dark phase. In opposite direction, GSK-J1 (0.1, 1.0, or 10 mg/kg, i.p.) injected at the beginning of the lights-on period induced no statistical changes in W, SWS, or REMS whereas if administered at darkness, we found a diminution in W and an enhancement in SWS and REMS. Finally, brain microdialysis experiments in freely moving animals were used to evaluate the effects of DZNep or GSK-J1 treatments on contents of sleep-related neurochemicals. The results showed that DZNep boosted extracellular levels of dopamine, norepinephrine, epinephrine, serotonin, adenosine, and acetylcholine if injected at the beginning of the lights-on period whereas GSK-J1 exerted similar outcomes but when administered at darkness. In summary, DZNep and GSK-J1 may control the sleep-wake cycle and sleep-related neurochemicals through histone methylation/demethylation activity.
- Sleep disorders and genesPublication . Murillo-Rodríguez, Eric; Yamamoto, Tetsuya; Veras, André Barciela; Rocha, Nuno; Telles-Correira, Diogo; Machado, Sérgio; Monteiro, Diogo; Budde, Henning; Torterolo, PabloThe sleep-wake cycle is a neurobiological phenomenon that shows intervals of activity alternating with restfulness that appears with a periodicity approximating the 24h day-night cycle. The sleep-wake cycle is under the control of diverse neuroanatomical and neurochemical systems, including monoaminergic, cholinergic, adenosinergic among many other systems. In addition, neuroanatomical centers linked to sleep promotion, such as hypothalamus, project to the cerebral cortex, subcortical relays and brainstem. In addition, the sleep-wake cycle has been associated to aberrant features known as sleep disorders. Here, we will discuss the role of specific gene expression on sleep disturbances. Given the expansion of the knowledge in the sleep-wake cycle area, it is indeed ambitious to describe all the genetics involved in the sleep modulation. However, in this chapter we reviewed the current understanding of the sleep disorders and gene expression.
- The endocannabinoid system may modulate sleep disorders in agingPublication . Murillo-Rodríguez, Eric; Budde, Henning; Veras, André Barciela; Rocha, Nuno; Telles-Correia, Diogo; Monteiro, Diogo; Cid, Luis; Yamamoto, Tetsuya; Machado, Sérgio; Torterolo, PabloAging is an inevitable process that involves changes across life in multiple neurochemical, neuroanatomical, hormonal systems, and many others. In addition, these biological modifications lead to an increase in age-related sickness such as cardiovascular diseases, osteoporosis, neurodegenerative disorders, and sleep disturbances, among others that affect activities of daily life. Demographic projections have demonstrated that aging will increase its worldwide rate in the coming years. The research on chronic diseases of the elderly is important to gain insights into this growing global burden. Novel therapeutic approaches aimed for treatment of age-related pathologies have included the endocannabinoid system as an effective tool since this biological system shows beneficial effects in preclinical models. However, and despite these advances, little has been addressed in the arena of the endocannabinoid system as an option for treating sleep disorders in aging since experimental evidence suggests that some elements of the endocannabinoid system modulate the sleep-wake cycle. This article addresses this less-studied field, focusing on the likely perspective of the implication of the endocannabinoid system in the regulation of sleep problems reported in the aged. We conclude that beneficial effects regarding the putative efficacy of the endocannabinoid system as therapeutic tools in aging is either inconclusive or still missing.