Estrogen receptor α regulates the IKKs/NF-kB activity involved in the development of mechanical allodynia induced by REM sleep deprivation in rats.

Several signaling pathways that converge in NF-kB activation have been linked to developing and maintaining different types of pathological pain. In addition, some mechanisms implied in the establishment of chronic pain have been demonstrated to have a sex-dependent correlation. This study aimed to determine if the IKKs/NF-kB signaling pathway is involved in establishing REM sleep deprivation (REMSD) induced mechanical allodynia in rats and its possible regulation depending on estradiol and estrogen receptors. Intrathecal administration of BMS-345541 or minocycline, two drugs that reduce the IKKs/NF-kB activity, avoided the development of mechanical allodynia in female but not in male rats subjected to 48 h of REMSD. Ovariectomy in female rats abolished the effect of BMS-345541 and minocycline. Meanwhile, the 17-ß-estradiol restitution restored it. Intrathecal administration of MPP, a selective ERα antagonist, but not PHTPP, a selective ERß antagonist, avoided the effect of BMS-345541 in female rats without hormonal manipulation. In addition, the transient run-down of ERα in female rats abolished the effect of BMS-345541. All data suggest an important role of ERα as a regulator of the IKKs/NF-kB activity. REMSD increased the ERα protein expression in the dorsal root ganglia and the dorsal spinal cord in females but not in male rats. Interestingly, ERα activation or ERα overexpression allowed the effect of BMS-345541 in male rats. Data suggest an important regulatory role of ERα in the IKKs/NF-kB activity on establishing mechanical allodynia induced by REMSD in female rats.

History of symptoms consistent with REM sleep behavior disorder in a population with Parkinson's Disease.

REM Sleep Behavioral Disorder (RBD) is a parasomnia marked by the maintenance of muscle tone during REM sleep. Evidence has placed RBD as one of the possible prodromal stages of Parkinson's Disease (PD), but data on the proportion of people with PD who have had symptoms of RBD are limited. This study aimed to investigate the history of symptoms compatible with RBD in a population with PD. The sample was composed by 73 patients with clinically diagnosed PD being followed up at a reference outpatient setting, compared to 73 age- and sex-matched individuals with no PD. The evaluation of symptoms compatible with RBD was performed using the Brazilian version of the RBD Screening Questionnaire (RBDSQ). The prevalence of symptoms compatible with RBD was 65 % for PD and 10.09 % for controls. The RBDSQ score was significantly higher in the PD group (6.03 ± 0.35) in comparison to the control group (2.38 ± 0.23). The odds ratio for presenting previous RBD-compatible symptoms was 12.09 in favor of positive PD cases. PD diagnosis has the following diagnostic properties in relation to presenting RBD symptoms: sensitivity of 0.65, specificity of 0.86, positive predictive value of 0.82 and negative predictive value of 0.71. In conclusion, the proportion of PD patients showing RBD symptoms is high, corroborating the expected neuroprogression of the disease on a case-control design comprising outpatient PD cases. Clinical practitioners should include evaluations of RBD-compatible symptoms during the PD assessment and, if positive, forward to a sleep specialist.

Sleep disorder syndromes of post-acute sequelae of SARS-CoV-2 (PASC) / Long Covid.

INTRODUCTION: COVID-19 infection has resulted in a high prevalence of a post-infectious syndrome, known as post-acute sequelae of SARS-CoV-2 (PASC) or "Long COVID". PASC is a heterogeneous disease with a high prevalence of sleep disturbances, varying from an insomnia disorder to excessive daytime sleepiness. METHODS: Patients seen in the Covid Survivorship Program at the Beth Israel Deaconess Medical Center Boston, USA, were screened for sleep disorders as part of a comprehensive multi-system evaluation. Those who screened positive were referred for a comprehensive sleep evaluation in a dedicated COVID-19-Sleep clinic, followed by diagnostic sleep testing and treatment. This report summarizes patients who completed an American Academy of Sleep Medicine (AASM) accredited facility-based diagnostic evaluation. International Classification of Sleep Disorders 3rd Edition-Revised criteria were met for all diagnoses. RESULTS: In 42 patients with PASC, five categories of sleep disorder syndromes were observed following a sleep clinic evaluation, including obstructive sleep apnea, chronic insomnia disorder, primary hypersomnia, REM behavior disorder (RBD), and new onset circadian phase delay. Seven patients met criteria for idiopathic hypersomnia, and two had narcolepsy type 2. RBD patients were infected in three different waves; circadian disturbance patients were all infected in the winter wave of 2020/21, and the primary hypersomnolence group occurred during all waves, predominantly the initial wave of 2020. A peculiar form of insomnia was a persistent loss of sleep regularity. CONCLUSIONS: Specific sleep symptoms/syndromes are reported in this select group of patients with PASC/Long Covid. As new onset sleep complaints are prevalent in PASC, we recommend a complete clinical and investigative sleep evaluation for persistent severe sleep symptoms following COVID-19 infection.

Amyloid profile is associated with sleep quality in preclinical but not in prodromal Alzheimer's disease older adults.

BACKGROUND: Few studies have assessed whether neuropathological markers of AD in the preclinical and prodromal stages are associated with polysomnographic changes and obstructive sleep apnea (OSA). METHODS: This was a cross-sectional, case-control study of older adults (≥60 years) without relevant clinical and psychiatric comorbidities selected randomly from a cohort of individuals without dementia in a tertiary university hospital in São Paulo, Brazil. They underwent neuropsychological evaluation for clinical diagnosis and were allocated into two samples: cognitively unimpaired (CU) and mild cognitive impairment (MCI). Also, they underwent PET-PiB to determine the amyloid profile and all-night in-lab polysomnography. For each sample, we compared polysomnographic parameters according to the amyloid profile (A+ vs A-). RESULTS: We allocated 67 participants (mean age 73 years, SD 10,1), 70 % females, 14 ± 5 years of education, into two samples: CU (n = 28, 42.4 %) and MCI (n = 39, 57.6 %). In the CU sample, the group A+ (n = 9) showed worse sleep parameters than A- (n = 19) (lower total sleep time (p = 0.007), and sleep efficiency (p = 0.005); higher sleep onset latency (p = 0.025), wake time after sleep onset (p = 0.011), and arousal index (AI) (p = 0.007)), and changes in sleep structure: higher %N1 (p = 0.005), and lower %REM (p = 0.006). In the MCI sample, MCI A-had higher AI (p = 0.013), respiratory disturbance index (p = 0.025, controlled for age), and higher rates of severe OSA than A+. DISCUSSION: The amyloid profile was associated with polysomnographic markers of worse sleep quality in individuals with preclinical AD but not with prodromal AD, probably due to the higher frequencies of severe OSA.

Sleep loss impairs blood-brain barrier function: Cellular and molecular mechanisms.

Sleep is a physiological process that preserves the integrity of the neuro-immune-endocrine network to maintain homeostasis. Sleep regulates the production and secretion of hormones, neurotransmitters, cytokines and other inflammatory mediators, both at the central nervous system (CNS) and at the periphery. Sleep promotes the removal of potentially toxic metabolites out of the brain through specialized systems such as the glymphatic system, as well as the expression of specific transporters in the blood-brain barrier. The blood-brain barrier maintains CNS homeostasis by selectively transporting metabolic substrates and nutrients into the brain, by regulating the efflux of metabolic waste products, and maintaining bidirectional communication between the periphery and the CNS. All those processes are disrupted during sleep loss. Brain endothelial cells express the blood-brain barrier phenotype, which arises after cell-to-cell interactions with mural cells, like pericytes, and after the release of soluble factors by astroglial endfeet. Astroglia, pericytes and brain endothelial cells respond differently to sleep loss; evidence has shown that sleep loss induces a chronic low-grade inflammatory state at the CNS, which is associated with blood-brain barrier dysfunction. In animal models, blood-brain barrier dysfunction is characterized by increased blood-brain barrier permeability, decreased tight junction protein expression and pericyte detachment from the capillary wall. Blood-brain barrier dysfunction may promote defects in brain clearance of potentially neurotoxic metabolites and byproducts of neural physiology, which may eventually contribute to neurodegenerative diseases. This chapter aims to describe the cellular and molecular mechanisms by which sleep loss modifies the function of the blood-brain barrier.

Brief Psychoeducational and Cognitive Therapy for Nightmare Disorder (BPCT-ND).

In adults, nightmare disorder is related to sleep deprivation, drug consumption or abuse, or other comorbid sleep disorders such as insomnia or insufficient sleep syndrome. Behavioral treatment has solid scientific evidence in disorders such as insomnia and, more recently, parasomnias. The aim of the present study was to investigate the clinical effectiveness of a Brief Behavioral Telemedicine Therapy in Nightmare Disorder in a 23-year-old female patient. The procedure consisted of the case study, with pre and posttreatment measures as well as follow-up after 1 month; and the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Paris Arousal Disorders Severity Scale, and a sleep diary were applied. In parallel with changes recorded in the sleep diary, a decrease in nightmares, sleepiness, and insomnia symptoms was observed when the intervention was finished. The behavioral intervention was clinically effective; therefore, the present case report provides information on behavioral treatments for nightmare disorder.

Neuropsychopharmacological Induction of (Lucid) Dreams: A Narrative Review.

Lucid dreaming (LD) is a physiological state of consciousness that occurs when dreamers become aware that they are dreaming, and may also control the oneiric content. In the general population, LD is spontaneously rare; thus, there is great interest in its induction. Here, we aim to review the literature on neuropsychopharmacological induction of LD. First, we describe the circadian and homeostatic processes of sleep regulation and the mechanisms that control REM sleep with a focus on neurotransmission systems. We then discuss the neurophysiology and phenomenology of LD to understand the main cortical oscillations and brain areas involved in the emergence of lucidity during REM sleep. Finally, we review possible exogenous substances-including natural plants and artificial drugs-that increase metacognition, REM sleep, and/or dream recall, thus with the potential to induce LD. We found that the main candidates are substances that increase cholinergic and/or dopaminergic transmission, such as galantamine. However, the main limitation of this technique is the complexity of these neurotransmitter systems, which challenges interpreting results in a simple way. We conclude that, despite these promising substances, more research is necessary to find a reliable way to pharmacologically induce LD.

Spinal bestrophin-1 and anoctamin-1 channels have a pronociceptive role in the tactile allodynia induced by REM sleep deprivation in rats.

Bestrophin-1 and anoctamin-1 are members of the calcium-activated chloride channels (CaCCs) family and are involved in inflammatory and neuropathic pain. However, their role in pain hypersensitivity induced by REM sleep deprivation (REMSD) has not been studied. This study aimed to determine if anoctamin-1 and bestrophin-1 are involved in the pain hypersensitivity induced by REMSD. We used the multiple-platform method to induce REMSD. REM sleep deprivation for 48 h induced tactile allodynia and a transient increase in corticosterone concentration at the beginning of the protocol (12 h) in female and male rats. REMSD enhanced c-Fos and α2δ-1 protein expression but did not change activating transcription factor 3 (ATF3) and KCC2 expression in dorsal root ganglia and dorsal spinal cord. Intrathecal injection of CaCCinh-A01, a non-selective bestrophin-1 blocker, and T16Ainh-A01, a specific anoctamin-1 blocker, reverted REMSD-induced tactile allodynia. However, T16Ainh-A01 had a higher antiallodynic effect in male than female rats. In addition, REMSD increased bestrophin-1 protein expression in DRG but not in DSC in male and female rats. In marked contrast, REMSD decreased anoctamin-1 protein expression in DSC but not in DRG, only in female rats. Bestrophin-1 and anoctamin-1 promote pain and maintain tactile allodynia induced by REM sleep deprivation in both male and female rats, but their expression patterns differ between the sexes.

Structural Brain Correlates of Sleep Microstructure in Spinocerebellar Ataxia Type 2 and its Role on Clinical Phenotype.

The influence of brain atrophy on sleep microstructure in Spinocerebellar Ataxias (SCAs) has not been extensively explored limiting the use of these sleep traits as surrogate biomarkers of neurodegeneration and clinical phenotype. The objective of the study is to explore the relationship between sleep microstructure and brain atrophy in SCA2 and its role in the clinical phenotype. Fourteen SCA2 mutation carriers (7 pre-manifest and 7 manifest subjects) underwent polysomnographic, structural MRI, and clinical assessments. Particularly, markers of REM and non-REM sleep microstructure, measures of cerebellar and brainstem atrophy, and clinical scores were analyzed through correlation and mediation analyses. The sleep spindle activity exhibited a negative correlation with the number of trials required to complete the verbal memory test (VMT), and a positive correlation with the cerebellar volume, but the significance of the latter correlation did not survive multiple testing corrections. However, the causal mediation analyses unveiled that sleep spindle activity significantly mediates the association between cerebellar atrophy and VMT performance. Regarding REM sleep, both phasic EMG activity and REM sleep without atonia exhibited significant associations with pontine atrophy and disease severity measures. However, they did not demonstrate a causal mediation effect between the atrophy measures and disease severity. Our study provides evidence about the association of the pontocerebellar atrophy with sleep microstructure in SCA2 offering insights into the cerebellar involvement in cognition via the control of the sleep spindle activity. Therefore, our findings may help to understand the disease pathogenesis and to better characterize sleep microstructure parameters as disease biomarkers.Clinical trial registration number (TRN): No applicable.

Noribogaine acute administration in rats promotes wakefulness and suppresses REM sleep.

Ibogaine is a potent atypical psychedelic that has gained considerable attention due to its antiaddictive and antidepressant properties in preclinical and clinical studies. Previous research from our group showed that ibogaine suppresses sleep and produces an altered wakefulness state, which resembles natural REM sleep. However, after systemic administration, ibogaine is rapidly metabolized to noribogaine, which also shows antiaddictive effects but with a distinct pharmacological profile, making this drug a promising therapeutic candidate. Therefore, we still ignore whether the sleep/wake alterations depend on ibogaine or its principal metabolite noribogaine. To answer this question, we conducted polysomnographic recordings in rats following the administration of pure noribogaine. Our results show that noribogaine promotes wakefulness while reducing slow-wave sleep and blocking REM sleep, similar to our previous results reported for ibogaine administration. Thus, we shed new evidence on the mechanisms by which iboga alkaloids work in the brain.

Sleep Pattern Interference in the Cognitive Performance of Lusitano Horses.

Like most mammalian, polyphasic sleep, equine sleep can be divided into two phases: the REM (rapid eye movement) phase and the NREM (non-rapid eye movement) phase. For this study, a randomized crossover experiment was conducted using ten purebred Lusitano horses, all dressage athletes aged from three to seven years old. The horses were filmed before the intervention to characterize their sleep patterns. REM sleep deprivation was achieved by not letting the horses attain sternal or lateral recumbency for three consecutive days, totaling 72 h. A spatial memory task and a visual attention test were performed. A recording time of 48 h appeared to be long enough to characterize the sleep patterns of the stalled horses. The total recumbency time of the studied population was lower than that previously reported in horses. Although the recumbency times before and after the intervention were similar, there was a tendency shown by the delta (p = 0.0839) towards an increased time needed to resolve spatial memory tasks in the sleep-deprived group. Future studies may deepen the understanding of horse sleep requirements and patterns, and the effects of environmental changes on horse sleep.

Methods for REM Sleep Density Analysis: A Scoping Review.

Rapid eye movements (REM) sleep density is the parameter proposed to explain the variability in the amount of eye movements during REM sleep. Alterations in REM sleep density have been proposed as a screening criterion for individuals with depression and other mental health conditions, but its accuracy has not been properly evaluated. The lack of consensus and the variability of the methods used to score it reduces the external validity of the results, hindering an adequate analysis of its diagnostic accuracy and clinical applicability. This scoping review aimed to identify and quantify the methods used to score REM sleep density, describing their main characteristics. A literature search was conducted in PubMed, Scopus, PsycInfo, and Web of Science. Only studies with objective measures for REM sleep density analysis in individuals with depression were considered eligible. The final sample comprised 57 articles, covering 64 analyses of REM sleep density. The relative frequency methods were the predominant measurement parameter for analyzing REM sleep density across studies. The most frequently adopted REM estimation unit was the number of REM events followed by mini-epochs containing REM. The most common unit of measurement were frequency/time measures. The results demonstrate that there is no consistency in the methods used to calculate REM sleep density in the literature, and a high percentage of studies do not describe their methods in sufficient detail. The most used method was the number of REM episodes per minute of REM sleep, but its use is neither unanimous nor consensual. The methodological inconsistencies and omissions among studies limit the replicability, comparability, and clinical applicability of REM sleep density. Future guidelines should discuss and include a specific methodology for the scoring of REM sleep density, so it can be consensually implemented in clinical services and research.

REM sleep behavior disorder: update on diagnosis and management / Transtorno comportamental do sono REM: atualização no diagnóstico e manejo

Abstract REM sleep behavior disorder (RBD) is characterized by a loss of atonia of skeletal muscles during REM sleep, associated with acting out behaviors during dreams. Knowledge of this pathology is important to predict neurodegenerative diseases since there is a strong association of RBD with diseases caused by the deposition of alpha-synuclein in neurons (synucleinopathies), such as Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB). Proper diagnosis of this condition will enable the use of future neuroprotective strategies before motor and cognitive symptoms. Diagnostic assessment should begin with a detailed clinical history with the patient and bed partner or roommate and the examination of any recorded home videos. Polysomnography (PSG) is necessary to verify the loss of sleep atonia and, when documented, the behaviors during sleep. Technical recommendations for PSG acquisition and analysis are defined in the AASM Manual for the scoring of sleep and associated events, and the PSG report should describe the percentage of REM sleep epochs that meet the criteria for RWA (REM without atonia) to better distinguish patients with and without RBD. Additionally, PSG helps rule out conditions that may mimic RBD, such as obstructive sleep apnea, non-REM sleep parasomnias, nocturnal epileptic seizures, periodic limb movements, and psychiatric disorders. Treatment of RBD involves guidance on protecting the environment and avoiding injuries to the patient and bed partner/roommate. Use of medications are also reviewed in the article. The development of neuroprotective medications will be crucial for future RBD therapy.

Resumo O transtorno comportamental do sono REM (TCSREM) é caracterizado por uma perda de atonia dos músculos esqueléticos durante o sono REM, associada a comportamentos de atuação durante os sonhos. O conhecimento desse transtorno é importante como preditor de doenças neurodegenerativas, uma vez que existe uma forte associação de TCSREM com doenças causadas pela deposição de alfa-sinucleína nos neurônios, como a doença de Parkinson (DP), atrofia de múltiplos sistemas (MSA) e demência com corpos de Lewy (DLB). O diagnóstico adequado dessa condição permitirá o uso de futuras estratégias neuroprotetoras antes do aparecimento dos sintomas motores e cognitivos. A avaliação diagnóstica deve começar com uma história clínica detalhada com o paciente e acompanhante, além de exame de vídeos. A polissonografia (PSG) é necessária para verificar a perda da atonia do sono e, quando documentados, os comportamentos durante o sono. As recomendações técnicas para aquisição e análise de PSG são definidas no Manual da AASM (Scoring of sleep and associated events) e o relatório de PSG deve descrever a porcentagem de períodos de sono REM que atendem aos critérios para REM sem atonia. Além disso, a PSG ajuda a descartar condições que podem mimetizar o TCSREM, como apneia obstrutiva do sono, parassonias do sono não REM, crises epilépticas noturnas, movimentos periódicos dos membros e transtornos psiquiátricos. O tratamento do TCSREM envolve orientações sobre adaptações do ambiente para evitar lesões ao paciente e ao colega de quarto. Medicamentos utilizados são revistos no artigo, assim como o crucial desenvolvimento de medicamentos neuroprotetores.

Dissociation of Arousal Index Between REM and NREM Sleep in Elderly Adults with Cognitive Impairment, No Dementia: A Pilot Study.

BACKGROUND: Sleep disruption in elderly has been associated with an increased risk of cognitive impairment and its transition into Alzheimer's disease (AD). High arousal indices (AIs) during sleep may serve as an early-stage biomarker of cognitive impairment non-dementia (CIND). OBJECTIVE: Using full-night polysomnography (PSG), we investigated whether CIND is related to different AIs between NREM and REM sleep stages. METHODS: Fourteen older adults voluntarily participated in this population-based study that included Mini-Mental State Examination, Neuropsi battery, Katz Index of Independence in Activities of Daily Living, and single-night PSG. Subjects were divided into two groups (n = 7 each) according to their results in Neuropsi memory and attention subtests: cognitively unimpaired (CU), with normal results; and CIND, with -2.5 standard deviations in memory and/or attention subtests. AIs per hour of sleep during N1, N2, N3, and REM stages were obtained and correlated with Neuropsi total score (NTS). RESULTS: AI (REM)  was significantly higher in CU group than in CIND group. For the total sample, a positive correlation between AI (REM)  and NTS was found (r = 0.68, p = 0.006), which remained significant when controlling for the effect of age and education. In CIND group, the AI (N2)  was significantly higher than the AI (REM) . CONCLUSION: In CIND older adults, this attenuation of normal arousal mechanisms in REM sleep are dissociated from the relative excess of arousals observed in stage N2. We propose as probable etiology an early hypoactivity at the locus coeruleus noradrenergic system, associated to its early pathological damage, present in the AD continuum.

The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson's Disease.

Patients with Parkinson's Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD we compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson's Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data, dementia, psychiatric conditions, or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score > 5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45-7.93), SNCA_A53T_rs104893877 (8.21, 2.26-36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08-4.10), and ZNF184_rs9468199 (1.89, 1.08-3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15-0.78). The ML algorithms led to similar results. The predictive models were highly specific (95-99%) but lacked sensitivity (9-39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop pRBD in PD. Additional investigations are needed.

Ibogaína: un psicodélico atípico con potencial antiadictivo / Ibogaine: an atypical psychedelic with anti-addictive potential

El trastorno por uso de sustancias es una enfermedad crónica de graves consecuencias. Actualmente, los tratamientos farmacológicos no apuntan a corregir los cambios neurobiológicos generados en el cerebro por el uso crónico de sustancias de abuso, sino que se enfocan principalmente en la atenuación de algunos de los síntomas que padece el consumidor. La ibogaína es un psicodélico atípico que, tanto en estudios observacionales como en ensayos clínicos abiertos, ha mostrado una propiedad antiadictiva que perdura en el tiempo. Sin embargo, su delicado perfil de toxicidad cardíaca, así como su uso en entornos sin adecuadas medidas de seguridad, han limitado su progresión en las investigaciones clínicas. Los efectos antiadictivos de ibogaína han disparado diversas líneas de investigación básica, preclínica y clínica, que buscan confirmar su efectividad, entender sus mecanismos de acción y delimitar su perfil de seguridad. Dada la poca información disponible para los profesionales de salud sobre esta sustancia, esta revisión busca aportar información acerca de su potencial terapéutico, posibles mecanismos de acción y riesgos asociados a su administración.

Substance use disorder is a chronic disease with severe consequences. Currently, pharmacological treatments do not aim to correct the neurobiological changes generated in the brain by the chronic use of substances of abuse, but rather focus mainly on attenuating some of the user's symptoms. Ibogaine is an atypical psychedelic that has shown long-lasting and interesting antiaddictive properties in both observational studies and open-label clinical trials. However, its delicate profile of cardiac toxicity, as well as its use in settings without adequate safety measures, have limited its progression in clinical research. The anti-addictive effects of ibogaine have triggered diverse scientific research in basic, preclinical, and clinical areas, which seek efficacy confirmation and to fully understand ibogaine´s underlying mechanisms of action and its safety profile. Given that there is little information available to health professionals about ibogaine and its antiaddictive properties, this review aims to provide published data about its therapeutic potential in drug addiction, its mechanisms of action, and risks associated with its administration.

Awake or Sleeping? Maybe Both A Review of Sleep-Related Dissociative States.

Recent studies have begun to understand sleep not only as a whole-brain process but also as a complex local phenomenon controlled by specific neurotransmitters that act in different neural networks, which is called "local sleep". Moreover, the basic states of human consciousness-wakefulness, sleep onset (N1), light sleep (N2), deep sleep (N3), and rapid eye movement (REM) sleep-can concurrently appear, which may result in different sleep-related dissociative states. In this article, we classify these sleep-related dissociative states into physiological, pathological, and altered states of consciousness. Physiological states are daydreaming, lucid dreaming, and false awakenings. Pathological states include sleep paralysis, sleepwalking, and REM sleep behavior disorder. Altered states are hypnosis, anesthesia, and psychedelics. We review the neurophysiology and phenomenology of these sleep-related dissociative states of consciousness and update them with recent studies. We conclude that these sleep-related dissociative states have a significant basic and clinical impact since their study contributes to the understanding of consciousness and the proper treatment of neuropsychiatric diseases.

¿Qué es el test de latencia múltiple de sueño y cuál es su uso en pediatría? / What is the multiple sleep latency test and what is its use in pediatrics?

La prueba de latencia múltiple del sueño nos permite evaluar objetivamente las variaciones normales y patológicas en la somnolencia y el estado de alerta. Es una prueba que evalúa qué tan rápido una persona se duerme en condiciones estandarizadas que facilitan el sueño, y se repite a intervalos de 2 horas durante todo el día. Es el estándar para documentar el inicio del sueño REM (SOREMP), que es un síntoma de narcolepsia y en la somnolencia idiopática podría ser útil. Su uso está ampliamente descrito en adultos, pero la prueba no es tan común en niños. En esta revisión, se analizan los valores en adultos y niños, y su utilidad, a partir de la historia de la prueba.

The multiple sleep latency test allows us to objectively assess normal and pathological variations in sleepiness and alertness. It is a test that assesses how quickly a person falls asleep under standardized conditions that facilitate sleep and is repeated at 2-h intervals throughout the day. is the standard for documenting sleep onset REM (SOREMP), which is a symptom of Narcolepsy and idiopathic sleepiness could be useful. Its use is widely described in adults, but the test is not so common in children. In this review, we analyze the values in adults and children, and their usefulness, based on from the history of the test.

Benzodiazepines and Sleep Architecture: A Systematic Review.

BACKGROUND: Insomnia, defined as a difficulty in initiating or maintaining sleep, is a relevant medical issue. Benzodiazepines (BZDs) are commonly prescribed to treat insomnia. Two phases characterize human sleep structure: sleep with Non-Rapid Eye Movement (NREM) and sleep with Rapid Eye Movement (REM). Physiological sleep includes NREM and REM phases in a continuous cycle known as "Sleep Architecture." OBJECTIVE: This systematic review summarizes the studies that have investigated effects of BZDs on Sleep Architecture. METHODS: The articles selection included human clinical trials (in English, Portuguese, or Spanish) only, specifically focused on BZDs effects on sleep architecture. PubMed, BVS, and Google Scholar databases were searched. RESULTS: Findings on BZDs effects on sleep architecture confirm an increase in stage 2 of NREM sleep and a decrease in time of stages 3 and 4 of NREM sleep with a reduction in time of REM sleep during the nocturnal sleep. CONCLUSION: Variations in NREM and REM sleep may lead to deficits in concentration and working memory and weight gain. The increase in stage 2 of NREM sleep may lead to a subjective improvement of sleep quality with no awakenings. BZDz should be prescribed with zeal and professional judgment. These patients should be closely monitored for possible long-term side effects.

The Role of Neuroglobin in the Sleep-Wake Cycle.

Neuroglobin (Ngb) is a protein expressed in the central and peripherical nervous systems of the vertebrate. The Ngb has different functions in neurons, including regulating O 2 homeostasis, oxidative stress, and as a neuroprotector after ischemia/hypoxia events. The Ngb is a hemoprotein of the globin family, structurally like myoglobin and hemoglobin. Ngb has higher expression in the cortex, hypothalamus, thalamus, brainstem, and cerebellum in mammals. Interestingly, Ngb immunoreactivity oscillates according to the sleep-wake cycle and decreases after 24 hours of sleep deprivation, suggesting that sleep homeostasis regulates Ngb expression. In addition, Ngb expresses in brain areas related to REM sleep regulation. Therefore, in the present review, we discuss the potential role of the Ngb in the sleep-wake regulation of mammals.