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RATIONALE: The nuclear receptor retinoid X receptor (RXR) belongs to a nuclear receptor superfamily that modulates diverse functions via homodimerization with itself or several other nuclear receptors, including PPARα. While the activation of PPARα by natural or synthetic agonists regulates the sleep-wake cycle, the role of RXR in the sleep modulation is unknown. OBJECTIVES: We investigated the effects of bexarotene (Bexa, a RXR agonist) or UVI 3003 (UVI, a RXR antagonist) on sleep, sleep homeostasis, levels of neurochemical related to sleep modulation, and c-Fos and NeuN expression. METHODS: The sleep-wake cycle and sleep homeostasis were analyzed after application of Bexa or UVI. Moreover, we also evaluated whether Bexa or UVI could induce effects on dopamine, serotonin, norepinephrine epinephrine, adenosine, and acetylcholine contents, collected from either the nucleus accumbens or basal forebrain. In addition, c-Fos and NeuN expression in the hypothalamus was determined after Bexa or UVI treatments. RESULTS: Systemic application of Bexa (1 mM, i.p.) attenuated slow-wave sleep and rapid eye movement sleep. In addition, Bexa increased the levels of dopamine, serotonin, norepinephrine epinephrine, adenosine, and acetylcholine sampled from either the nucleus accumbens or basal forebrain. Moreover, Bexa blocked the sleep rebound period after total sleep deprivation, increased in the hypothalamus the expression of c-Fos, and decreased NeuN activity. Remarkably, UVI 3003 (1 mM, i.p.) induced opposite effects in sleep, sleep homeostasis, neurochemicals levels, and c-Fos and NeuN activity. CONCLUSIONS: The administration of RXR agonist or antagonist significantly impaired the sleep-wake cycle and exerted effects on the levels of neurochemicals related to sleep modulation. Moreover, Bexa or UVI administration significantly affected c-Fos and NeuN expression in the hypothalamus. Our findings highlight the neurobiological role of RXR on sleep modulation.

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Aging 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.

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Lattari, E, Campos, C, Lamego, MK, Legey, S, Neto, GM, Rocha, NB, Oliveira, AJ, Carpenter, CS, and Machado, S. Can transcranial direct current stimulation improve muscle power in individuals with advanced weight-training experience? J Strength Cond Res 34(1): 97-103, 2020-The aim of this study was to investigate the effects of transcranial direct current stimulation (tDCS) on countermovement jump (CMJ) performance in men with advanced strength-training experience. Ten healthy male subjects with advanced strength training and squatting exercise experience were included. Participants took part in an initial visit to the laboratory to complete anthropometric measurements and CMJ kinematic test-retest reliability. Participants then completed 3 experimental conditions, 48-72 hours apart, in a randomized, double-blinded crossover design: anodal, cathodal, and sham-tDCS (2 mA for 20 minutes targeting the motor cortex bilaterally). Participants completed 3 CMJ tests before and after each experimental condition, with 1-minute recovery interval between each test. The best CMJ in each moment was selected for analysis. Two-way (condition by moment) repeated measures analysis of variance was performed for CMJ height, flight time (FT), and muscular peak power (PP). Effect sizes and interindividual variability of tDCS responses were also analyzed. There was a significant condition by moment interaction for all outcome measures, with a large prepost increase in CMJ height, FT, and PP in the anodal condition. All the participants displayed CMJ performance improvements after the anodal condition. There were no significant differences in both cathodal and sham conditions. Anodal tDCS may be a valuable tool to enhance muscle power-related tasks performance, which is extremely relevant for sports that require vertical jumping ability. Anodal tDCS may also be used to support strength training, enhancing its effects on performance-oriented outcome measures.

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Lattari, E, Rosa Filho, BJ, Fonseca Junior, SJ, Murillo-Rodriguez, E, Rocha, N, Machado, S, and Maranhão Neto, GA. Effects on volume load and ratings of perceived exertion in individuals' advanced weight training after transcranial direct current stimulation. J Strength Cond Res 34(1): 89-96, 2020-The aim of this study was investigate the effects of transcranial direct current stimulation (tDCS) on volume load and ratings of perceived exertion. Fifteen young healthy individuals, aged between 20 and 30 years in advanced strength training were recruited. Test and retest of the 10 maximum repetitions (10RM) were performed to determine the reliability of load used. Subjects performed 3 experimental conditions in a randomized, double-blinded crossover design: anodic stimulation (a-tDCS), cathodic stimulation (c-tDCS), and sham (2 mA for 20 minutes targeting the dorsolateral prefrontal cortex left). Immediately after the experimental conditions, subjects completed 1 set of maximum repetitions with 10RM load (volume load) and answered to OMNI-RES (poststimulation) (level of significance p ≤ 0.05). The volume load showed main effect for condition (F(2, 28) = 164.801; p < 0.001). In poststimulation, a-tDCS was greater than c-tDCS (p ≤ 0.001) and sham (p ≤ 0.001). For ratings of perceived exertion (OMNI-RES), the results showed main effect for condition (F(2, 28) = 9.768; p ≤ 0.05). In poststimulation, c-tDCS was greater than a-tDCS (p ≤ 0.05) and sham (p ≤ 0.05). We conclude that the use of a-tDCS may promote increase in volume load for the LP45 exercise. Moreover, higher volume loads are necessary to maximize muscle strength and anabolism.

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Histone 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]-ß-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.

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Hallucination-like experiences (HLEs) are typically defined as sensory perceptions in the absence of external stimuli. Multidimensional tools, able to assess different facets of HLEs, are helpful for a better characterization of hallucination proneness and to investigate the cross-national variation in the frequencies of HLEs. The current study set out to establish the validity, factor structure, and measurement invariance of the Launay-Slade Hallucinations Scale-Extended (LSHS-E), a tool to assess HLEs. A total of 4419 respondents from 10 countries were enrolled. Network analyses between the LSHS-E and the 3 dimensions of the Community Assessment of Psychic Experiences (CAPE) were performed to assess convergent and divergent validity of the LSHS-E. Confirmatory factor analysis was used to test its measurement invariance. The best fit was a 4-factor model, which proved invariant by country and clinical status, indicating cross-national stability of the hallucination-proneness construct. Among the different components of hallucination-proneness, auditory-visual HLEs had the strongest association with the positive dimension of the CAPE, compared with the depression and negative dimensions. Participants who reported a diagnosis of a mental disorder scored higher on the 4 LSHS-E factors. Small effect size differences by country were found in the scores of the 4 LSHS-E factors even after taking into account the role of socio-demographic and clinical variables. Due to its good psychometric properties, the LSHS-E is a strong candidate tool for large investigations of HLEs.

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Cannabis sativa is a plant that contains more than 500 components, of which the most studied are Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Several studies have indicated that CBD displays neurobiological effects, including wake promotion. Moreover, experimental evidence has shown that injections of CBD enhance wake-related compounds, such as monoamines (dopamine, serotonin, epinephrine, and norepinephrine). However, no clear evidence is available regarding the effects of CBD on additional wake-related neurochemicals such as acetylcholine (ACh). Here, we demonstrate that systemic injections of CBD (0, 5, 10 or 30 mg/kg, i.p.) at the beginning of the lights-on period, increase the extracellular levels of ACh collected from the basal forebrain and measured by microdialysis and HPLC means. Moreover, the time course effects on the contents of ACh were present 5 h post-injection of CBD. Altogether, these data demonstrate that CBD increases ACh levels in a brain region related to wake control. This study is the first to show the effects of ACh levels in CBD-treated rats and suggests that the basal forebrain might be a site of action of CBD for wakefulness modulation.

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The 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.

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BACKGROUND: National projections about the increase in the elderly population over 60 years bring with it an increase in the number of people affected by Parkinson's Disease (PD), making it an important public health problem. Therefore, the establishment of effective strategies for intervention in people with PD needs to be more clearly investigated. OBJECTIVE: The study aimed to report the effectiveness of exercise on functional capacity and neurobiological mechanisms in people with PD. METHODS: This study is a critical review of the literature. RESULTS: The progressive death of dopaminergic neurons in the substantia nigra is described as one of the main physiological mechanisms manifested before PD, directly interfering with motor behavior. However, PD is not only related to motor symptoms, but also to cognitive, autonomic, and mood impairments. Such effects may be attenuated by pharmacological influence, but also evidence suggests that the implementation of regular physical exercise programs may exhibit potential benefits over PD. The synthesis and expression of monoaminergic neurotransmitters can act positively on motor disorders, as well as directly or indirectly influence the neuronal plasticity of the brain, restoring neuronal pathways previously affected. CONCLUSION: Physical exercise contributes effectively to the treatment of PD, and can play a preventive and maintenance role of physical fitness and mental health.

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INTRODUCTION: Mental health decline is one of the main responsible factors for augments in health care costs, and diagnosis of Alzheimer's disease (AD). Some studies stated physical exercise is useful for reduction in cognitive decline and AD. Moreover, a recent review argued that evidence are scarce due to few studies published and lack of configuration information of exercise protocol, such as intensity and duration of exercise, number of sessions and other relevant data, to allow appropriate assessment. MATERIALS AND METHODS: Here, we discussed the possible confounders or factors responsible for these differences and possible neurophysiological mechanisms. RESULTS: Most studies revealed a possible positive association between physical exercise and cognitive assessments. There are inconsistencies in studies design responsible for varying use of cognitive assessments and different assessments of fitness. However, these studies do not fail to provide evidence about the benefits of exercise, but fail to make it possible because of the lack of dose-response information in AD patients. Physical exercise of moderate intensity should be considered as standard recommendation to reduce cognitive decline, probably due to the improvement in neurodegenerative mechanisms, and the increase in neuroplastic and neuroprotective neurotrophic factors. CONCLUSION: Therefore, it is suggested that physical exercise is an important neuroprotective modulator, bringing significant control of the disease and amplifying brain functions.