Association between Acute Respiratory Distress Syndrome Due to COVID-19 and Long-Term Sleep and Circadian Sleep-Wake Disorders.

Current studies agree on the impact of sleep and circadian rest-activity rhythm alterations in acute respiratory distress syndrome (ARDS) survivors. However, research on the duration of this impact is scarce. In this study, we evaluate the impact of ARDS on the sleep and circadian rest-activity rhythm of COVID-19 survivors twelve months after hospital discharge. This is a prospective study including COVID-19 survivors with and without ARDS during hospitalization. Data was collected four and twelve months after hospital discharge. The interventions included one-week wrist actigraphy and a home sleep apnea test (HSAT), and evaluations were conducted according to the Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), and insomnia severity index (ISI). Fifty-two patients were evaluated (ARDS = 31 and non-ARDS = 21); they had a median age of 49.0 [39.0;57.2] years and 53.8% were male. After twelve months, 91.3% presented poor sleep quality, 58.7% presented insomnia, 50% presented daytime somnolence, and 37% presented comorbid insomnia and obstructive sleep apnea (COMISA). No significant improvement was observed in relation to sleep or the circadian rest-activity rhythm between four and twelve months. A tendency of poor sleep quality, insomnia, daytime somnolence, and COMISA was observed. Finally, there was no significant impact on the circadian rest-activity rhythm between four and twelve months or between the groups.

Folic Acid and Vitamin B12 Prevent Deleterious Effects of Rotenone on Object Novelty Recognition Memory and Kynu Expression in an Animal Model of Parkinson's Disease.

Parkinson's disease (PD) is characterized by a range of motor signs, but cognitive dysfunction is also observed. Supplementation with folic acid and vitamin B12 is expected to prevent cognitive impairment. To test this in PD, we promoted a lesion within the substantia nigra pars compacta of rats using the neurotoxin rotenone. In the sequence, the animals were supplemented with folic acid and vitamin B12 for 14 consecutive days and subjected to the object recognition test. We observed an impairment in object recognition memory after rotenone administration, which was prevented by supplementation (p < 0.01). Supplementation may adjust gene expression through efficient DNA methylation. To verify this, we measured the expression and methylation of the kynureninase gene (Kynu), whose product metabolizes neurotoxic metabolites often accumulated in PD as kynurenine. Supplementation prevented the decrease in Kynu expression induced by rotenone in the substantia nigra (p < 0.05), corroborating the behavioral data. No differences were observed concerning the methylation analysis of two CpG sites in the Kynu promoter. Instead, we suggest that folic acid and vitamin B12 increased global DNA methylation, reduced the expression of Kynu inhibitors, maintained Kynu-dependent pathway homeostasis, and prevented the memory impairment induced by rotenone. Our study raises the possibility of adjuvant therapy for PD with folic acid and vitamin B12.

Impact of Obstructive Sleep Apnea (OSA) in COVID-19 Survivors, Symptoms Changes Between 4-Months and 1 Year After the COVID-19 Infection.

Objective: To determine the association between Obstructive Sleep Apnea (OSA) with long-term symptoms and inflammatory cytokines, exploring the changes between 4-months and 1-year after COVID-19 infection. Methods: We conducted an observational, prospective cohort study, including patients ≥18 years old with confirmed diagnosis of COVID-19 between April to July 2020. All participants underwent two clinical follow-up visits, the first at 4-months (Visit 1) and the second at 1 year, after SARS-CoV-2 infection (Visit 2). Plasma glucose, total cholesterol, HDL, and triglycerides. Regarding pulmonary function, spirometry and lung diffusion capacity tests were assessed. For mental and neurocognitive evaluation, a short-form (SF-12), Beck depression and Hospital-Anxiety depression questionnaires were conducted at both time-points, whereas the Montreal Cognitive assessment was conducted during the second follow-up. Regarding to sleep evaluation, Epworth Sleepiness Scale, Insomnia Severity index and STOP-BANG questionnaire were conducted. Additionally, a home sleep apnea test and 7-day wrist actigraphy were performed in all participants. Inflammatory cytokines were measured using an inflammatory cytokine bead array kit. p-values < 0.05 were considered statistically significant and statistical analyses were performed using R software. Results: A total of 60 patients were included in the first follow-up, from which 57 completed the second follow-up. The mean age was 46.4 years-old (SD ± 13.1) and 53.3% were male. 30% of cases reported mild COVID-19 infection, 28.3% with moderate illness, and 41.6% with severe illness. Moreover, 56.6% of them were admitted to the ICU. Regarding to metabolic values, the OSA group showed higher values of insulin resistance (IR) (27%), systolic blood pressure (SBP) 135.2 (±19.1), dyslipidemia (67.5%), total cholesterol 202.1 (±60.5), triglycerides 176.1 (±119.0) and HOMA-IR 9.0 (±18.8) in comparison with the non-OSA group. 1 year after COVID-19 infection, DLCO test remains abnormal in OSA patients (25% OSA vs. 3.6% non-OSA, p = 0.02). Finally, those participants with OSA who develop ARDS reported an adjusted OR 20.4 (95%-CI, 1.04-504) risk of neurocognitive impairment. Discussion: Among patients with previous COVID-19, OSA impact the development of incident glycemic, neurocognitive impairment, and abnormal functional pulmonary changes that persist up to 1 year since acute phase.

Sleep health and the circadian rest-activity pattern four months after COVID-19.

OBJECTIVE: To describe the prevalence and severity of sleep disorders and circadian alterations in COVID-19 patients four months after the acute phase of the disease. METHODS: This was a cross-sectional observational prospective study of patients with mild COVID-19, moderate COVID-19 (requiring hospitalization but no mechanical ventilation), or severe COVID-19 (with ARDS) four months after the acute phase of the disease. All patients underwent a home sleep apnea test and seven-day wrist actigraphy, as well as completing questionnaires to assess sleep quality and mental health. Differences among the three groups of patients were evaluated by ANOVA and the chi-square test. RESULTS: A total of 60 patients were included in the study. Of those, 17 were in the mild COVID-19 group, 18 were in the moderate COVID-19 group, and 25 were in the severe COVID-19 group. Sleep quality, as assessed by satisfaction, alertness, timing, efficiency, and duration scale scores, was found to be impaired in all three groups, which also had a high prevalence of unhealthy sleep, as assessed by the Pittsburgh Sleep Quality Index. The prevalence of insomnia was increased in all three groups, as assessed by the Insomnia Severity Index. The home sleep apnea test showed that the overall prevalence of obstructive sleep apnea was 60%, and seven-day wrist actigraphy showed that total sleep time was < 7 h in all three groups. Changes in quality of life and in the circadian rest-activity pattern were observed in all three groups. CONCLUSIONS: Sleep-related symptoms, changes in the circadian rest-activity pattern, and impaired mental health appear to be common in COVID-19 patients four months after the acute phase of the disease, severe COVID-19 being associated with a higher prevalence of obstructive sleep apnea.

Ludic Table: a comparative study between playful rehabilitation and kinesiotherapy in restricting upper limb movements in individuals with stroke.

Stroke is a neurological syndrome resulting from the sudden interruption of blood flow. Among the symptoms/consequences of the stroke are muscle weakness in the lower and/or upper limbs, decreased sensitivity, altered fine motor skills, proprioception, and reflections. The treatment for the motor consequences is orthopedic management, in which the physiotherapist assists the individual in repetitive range of motion exercises, which can be demotivating during the treatment. The Ludic Table (LT), on the other hand, incorporates playfulness into therapy, making it a motivating tool. This research describes the comparative study between kinesiotherapy techniques and exercises using the LT, applied to the development of upper limb movements. For this, fourteen volunteers were divided into groups, submitted to interventions according to the techniques, and evaluated using systems such as goniometry, HAQ-DI, GMFM-88, and neurofunctional assessment. In general, it can be stated that regardless of the intervention, the individuals obtained gain in movements (minimum average of 7 degrees) and that the use of the LT allows the development of the angular amplitude and the reduction of the effects of spasticity. The individuals submitted to the intervention through the LT obtained the development of a greater number of articular movements of the shoulder and elbow.

Sleep health and the circadian rest-activity pattern four months after COVID-19 / Saúde do sono e o padrão circadiano de atividade e repouso quatro meses depois da COVID-19

ABSTRACT Objective: To describe the prevalence and severity of sleep disorders and circadian alterations in COVID-19 patients four months after the acute phase of the disease. Methods: This was a cross-sectional observational prospective study of patients with mild COVID-19, moderate COVID-19 (requiring hospitalization but no mechanical ventilation), or severe COVID-19 (with ARDS) four months after the acute phase of the disease. All patients underwent a home sleep apnea test and seven-day wrist actigraphy, as well as completing questionnaires to assess sleep quality and mental health. Differences among the three groups of patients were evaluated by ANOVA and the chi-square test. Results: A total of 60 patients were included in the study. Of those, 17 were in the mild COVID-19 group, 18 were in the moderate COVID-19 group, and 25 were in the severe COVID-19 group. Sleep quality, as assessed by satisfaction, alertness, timing, efficiency, and duration scale scores, was found to be impaired in all three groups, which also had a high prevalence of unhealthy sleep, as assessed by the Pittsburgh Sleep Quality Index. The prevalence of insomnia was increased in all three groups, as assessed by the Insomnia Severity Index. The home sleep apnea test showed that the overall prevalence of obstructive sleep apnea was 60%, and seven-day wrist actigraphy showed that total sleep time was < 7 h in all three groups. Changes in quality of life and in the circadian rest-activity pattern were observed in all three groups. Conclusions: Sleep-related symptoms, changes in the circadian rest-activity pattern, and impaired mental health appear to be common in COVID-19 patients four months after the acute phase of the disease, severe COVID-19 being associated with a higher prevalence of obstructive sleep apnea.

RESUMO Objetivo: Descrever a prevalência e gravidade de transtornos do sono e alterações circadianas em pacientes com COVID-19 quatro meses depois da fase aguda da doença. Métodos: Estudo prospectivo observacional transversal com pacientes com COVID-19 leve, moderada (com necessidade de hospitalização, mas não de ventilação mecânica) ou grave (com SDRA) quatro meses depois da fase aguda da doença. Todos os pacientes foram submetidos a teste domiciliar de apneia do sono e actigrafia de sete dias, além de terem preenchido questionários para avaliar a qualidade do sono e a saúde mental. As diferenças entre os três grupos foram avaliadas por meio de ANOVA e teste do qui-quadrado. Resultados: Foram incluídos no estudo 60 pacientes. Destes, 17 eram do grupo COVID-19 leve, 18 do grupo COVID-19 moderada e 25 do grupo COVID-19 grave. A qualidade do sono, avaliada pela pontuação na escala satisfaction, alertness, timing, efficiency, and duration, foi prejudicada nos três grupos, que também apresentaram alta prevalência de sono não saudável, pelo Índice de Qualidade do Sono de Pittsburgh. A prevalência de insônia, avaliada pelo Insomnia Severity Index, foi elevada nos três grupos. O teste domiciliar de apneia do sono mostrou que a prevalência geral de apneia obstrutiva do sono foi de 60%, e a actigrafia de sete dias mostrou que o tempo total de sono foi < 7 h nos três grupos. Alterações da qualidade de vida e do padrão circadiano de atividade e repouso foram observadas nos três grupos. Conclusões: Sintomas relacionados ao sono, alterações do padrão circadiano de atividade e repouso e comprometimento da saúde mental parecem ser comuns em pacientes com COVID-19 quatro meses depois da fase aguda da doença, sendo a COVID-19 grave associada a uma maior prevalência de apneia obstrutiva do sono.

Disruption of neocortical synchronisation during slow-wave sleep in the rotenone model of Parkinson's disease.

Parkinson's disease motor dysfunctions are associated with improperly organised neural oscillatory activity. The presence of such disruption at the early stages of the disease in which altered sleep is one of the main features could be a relevant predictive feature. Based on this, we aimed to investigate the neocortical synchronisation dynamics during slow-wave sleep (SWS) in the rotenone model of Parkinson's disease. After rotenone administration within the substantia nigra pars compacta, one group of male Wistar rats underwent sleep-wake recording. Considering the association between SWS oscillatory activity and memory consolidation, another group of rats underwent a memory test. The fine temporal structure of synchronisation dynamics was evaluated by a recently developed technique called first return map. We observed that rotenone administration decreased the time spent in SWS and altered the power spectrum within different frequency bands, whilst it increased the transition rate from a synchronised to desynchronised state. This neurotoxin also increased the probability of longer and decreased the probability of shorter desynchronisation events. At the same time, we observed impairment in object recognition memory. These findings depict an electrophysiological fingerprint represented by a disruption in the typical oscillatory activity within the neocortex at the early stages of Parkinson's disease, concomitant with a decrease in the time spent in SWS and impairment in recognition memory.

MT2 melatonin receptors expressed in the olfactory bulb modulate depressive-like behavior and olfaction in the 6-OHDA model of Parkinson's disease.

Melatonin MT1 and MT2 receptors are expressed in the glomerular layer of the olfactory bulb (OB); however, the role of these receptors has not been evaluated until now. Considering the association of the OB with olfactory and depressive disorders in Parkinson's disease (PD), we sought to investigate the involvement of melatonin receptors in these non-motor disturbances in an intranigral 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD. We demonstrate the presence of functional melatonin receptors in dopaminergic neurons of the glomerular layer. Local administration of melatonin (MLT, 1 µg/µl), luzindole (LUZ, 5 µg/µl) or the MT2-selective receptor drug 4-P-PDOT (5 µg/µl) reversed the depressive-like behavior elicited by 6-OHDA. Sequential administration of 4-P-PDOT and MLT (5 µg/µl, 1 µg/µl) promoted additive antidepressant-like effects. In the evaluation of olfactory discrimination, LUZ induced an olfactory impairment when associated with the nigral lesion-induced impairment. Thus, our results suggest that melatonin MT2 receptors expressed in the glomerular layer are involved in depressive-like behaviors and in olfactory function associated with PD.

Pain impairs consolidation, but not acquisition or retrieval of a declarative memory.

Among the physical conditions that impair memory performance, pain is one of the most prevalent. However, the mechanisms by which pain impairs memory are largely unknown. In this study, we asked whether pain affects memory acquisition, consolidation and retrieval as well as whether memory impairment depends on pain intensity. Wistar rats received a hind paw injection of formalin (1%) at different phases of object recognition test. The injection of formalin after training but not before training or testing impaired object recognition memory. We concluded that pain impairs the consolidation but not acquisition or retrieval of object recognition memory, which is a subtype of declarative memory. Morphine, at a dose that did not affect object recognition memory in control rats, drastically reduced formalin-induced nociceptive behavior without reversing memory impairment. A lower dose of formalin (0.25%) induced less nociceptive behavior, but similar memory impairment. There is no statistical correlation between the intensity of nociceptive response and the performance in object recognition test. However, when formalin-induced nociceptive response was blocked by a local anesthetic, memory impairment was prevented. These findings suggest that pain-induced impairment in the consolidation of object recognition memory does not directly depend on the intensity of nociceptive activity.

Increased Mmp/Reck Expression Ratio Is Associated with Increased Recognition Memory Performance in a Parkinson's Disease Animal Model.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Among its non-motor symptoms, sleep disorders are extremely common, being linked to cognitive and memory disruption. The microenvironment, particularly the extracellular matrix (ECM), is deeply involved in memory consolidation as well as in neuropathological processes, such as inflammation, damage to the blood-brain barrier and neuronal death. To better understand ECM dynamics in PD memory disturbances, we investigated the orchestrated expression of Mmps (Mmp-3, Mmp-7, and Mmp-9) and their modulators (Reck and Timp-3) in a rotenone-induced PD model. Also, we introduced an additional intervention in the memory process through rapid eye movement sleep deprivation (REMSD). We observed a REMSD-induced trend in reversing the memory impairment caused by rotenone administration. Associated to this phenotype, we observed a significant increase in Mmp-7/Reck and Mmp-9/Reck mRNA expression ratio in the substantia nigra and Mmp-9/Reck ratio in the hypothalamus. Moreover, the positive correlation of Mmp/Reck expression ratios between the substantia nigra and the striatum, observed upon rotenone infusion, was reversed by REMSD. Taken together, our results suggest a potential orchestrated association between an increase in Mmp-7 and Mmp-9/Reck expression ratios in the substantia nigra and a possible positive effect on cognitive performance in subjects affected by PD.

Potential new therapies against a toxic relationship: neuroinflammation and Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder classically associated with motor symptoms, but several nonmotor disturbances appear decades before the clinical diagnosis of the disease. A variety of hypotheses exist to explain the onset of PD, and neuroinflammation is one of the most investigated processes. In fact, strong evidence suggests that PD begins with an inflammatory process; currently, however, no anti-inflammatory therapy is clinically employed to alleviate the typical motor and the prodromal disturbances such as olfactory loss, cognitive impairments, depression and anxiety, sleep disturbances, and autonomic disorders. In fact, the classical dopaminergic therapies are not effective in alleviating these symptoms and there is no other specific therapy for these outcomes. Therefore, in this review, we will discuss novel potential pharmacological therapeutic strategies focusing on cannabinoids, caffeine, melatonin, and dietary compounds, which could act as adjuvants to regular PD therapy. These described chemicals have been extensively investigated as anti-inflammatory agents possibly promoting beneficial effects on nonmotor symptoms of PD. The investigation of the inflammatory process at different stages of PD progression should give us a better view of the therapeutic scenario and could improve our understanding of the mechanisms of this disease.

Chronic sleep restriction in the rotenone Parkinson's disease model in rats reveals peripheral early-phase biomarkers.

Parkinson's disease (PD) is a chronic disorder that presents a range of premotor signs, such as sleep disturbances and cognitive decline, which are key non-motor features of the disease. Increasing evidence of a possible association between sleep disruption and the neurodegenerative process suggests that sleep impairment could produce a detectable metabolic signature on the disease. In order to integrate neurocognitive and metabolic parameters, we performed untargeted and targeted metabolic profiling of the rotenone PD model in a chronic sleep restriction (SR) (6 h/day for 21 days) condition. We found that SR combined with PD altered several behavioural (reversal of locomotor activity impairment; cognitive impairment; delay of rest-activity rhythm) and metabolic parameters (branched-chain amino acids, tryptophan pathway, phenylalanine, and lipoproteins, pointing to mitochondrial impairment). If combined, our results bring a plethora of parameters that represents reliable early-phase PD biomarkers which can easily be measured and could be translated to human studies.

Dopaminergic Lesion in the Olfactory Bulb Restores Olfaction and Induces Depressive-Like Behaviors in a 6-OHDA Model of Parkinson's Disease.

Olfactory impairments and depressive behavior are commonly reported by individuals with Parkinson's disease (PD) being observed before motor symptoms. The mechanisms underlying these clinical manifestations are not fully elucidated. However, the imbalance in dopaminergic neurotransmission seems to play an important role in this context. In patients and animal models of PD, an increase in the dopaminergic interneurons of the glomerular layer in olfactory bulb (OB-gl) is observed, which may contribute to the olfactory impairment. In addition, neuronal imbalance in OB is related to depressive symptoms, as demonstrated by chemical olfactory bulbectomy. In view of that, we hypothesized that a reduction in the number or density of dopaminergic neurons present in OB could promote an olfactory improvement and, in contrast, would accentuate the depressive-like behaviors in the 6-hydroxydopamine (6-OHDA) model of PD. Therefore, we performed single or double injections of 6-OHDA within the substantia nigra pars compacta (SNpc) and/or in the OB-gl. We observed that, after 7 days, the group with nigral lesion exhibited olfactory impairment, as well as the group with the lesion in the OB-gl. However, the combination of the lesions prevented the occurrence of hyposmia. In relation to depressive-like behaviors, we observed that the SNpc injury promoted depressive-like behavior, being accentuated after a double injury. Our results demonstrated the importance of the dopaminergic neurons of the OB-gl in different non-motor features of PD, since the selective reduction of these periglomerular neurons was able to induce olfactory impairment and depressive-like behaviors.

Olfaction in female Wistar rats is influenced by dopaminergic periglomerular neurons after nigral and bulbar lesions.

Hyposmia is found in Parkinsonian patients decades before the onset of motor disorders. The same occurs with sleep disorders, especially infuencing rapid eye movement (REM) sleep, which affect a large percentage of people who have Parkinson's disease. These two disturbances presumably are closely related to a dopaminergic dysfunction. Therefore, we propose that selective lesions, induced by rotenone, of the periglomerular neurons within the olfactory bulb or of the nigrostriatal pathway could result in hyposmia. In addition, we hypothesized that REM sleep deprivation (REMSD) could have potential to generate a synergistic olfactory impairment in both lesion paradigms. The results indicated that rotenone-induced nigrostriatal lesions in female Wistar rats were associated with odor preference changes, similar to hedonic tone impairment, but without a supposed potentiation triggered by REMSD. The nigrostriatal injury negatively affected olfaction performance, which was counteracted, functionally, by REMSD. However, injury to periglomerular neurons was less influenced by REMSD, as olfactory performance was restored after rebound sleep. We conclude that female rats present a pattern of olfactory discrimination/preference that is dependent on the activities of the nigrostriatal and the main olfactory pathways.

Fish oil supplementation reverses behavioral and neurochemical alterations induced by swimming exercise in rats.

Diet and exercise are known to affect learning and memory. However, the effects of these interventions in the brain under development remains to be better investigated as the effects of high-intensity exercise. Moreover, it is still unclear how long the influence of diet and exercise lasts after the interventions are ceased. To investigate this, juvenile Wistar rats (30 days old) were supplemented with fish oil rich in polyunsaturated fatty acids (PUFAs) and performed swimming training for 50 days, 45 min per day, 5 times/week. The animals were assessed for locomotor activity with the open field test and for spatial memory with the object location task. To investigate neurochemical parameters such as fatty acids incorporation within the plasma membrane and brain-derived neurotrophic factor (BDNF) levels, the animals were euthanized, and the hippocampus dissected. These investigations were made at the end of the supplementation and exercise protocols and 21 days after the protocol has ended. Results indicate that high-intensity exercise impaired the spatial memory and decreased the levels of BDNF. Although supplementation led to PUFAs incorporation in plasma membrane, it did not prevent the harmful effect of exercise on memory. After 21 days of interruption, we observed that the supplementation reversed not only the deleterious effect of exercise on memory but also increased the BDNF levels. These results point to a complex influence of diet and exercise on spatial memory of juvenile rats, persisting after 21 days of interruption.

Olfactory impairment is related to REM sleep deprivation in rotenone model of Parkinson's disease.

INTRODUCTION: Olfactory dysfunction affects about 85-90% of Parkinson's disease (PD) patients with severe deterioration in the ability of discriminate several types of odors. In addition, studies reported declines in olfactory performances during a short period of sleep deprivation. Besides, PD is also known to strongly affect the occurrence and maintenance of rapid eye movement (REM) sleep. METHODS: Therefore, we investigated the mechanisms involved on discrimination of a social odor (dependent on the vomeronasal system) and a non-social odor (related to the main olfactory pathway) in the rotenone model of PD. Also, a concomitant impairment in REM sleep was inflicted with the introduction of two periods (24 or 48 h) of REM sleep deprivation (REMSD). Rotenone promoted a remarkable olfactory impairment in both social and non-social odors, with a notable modulation induced by 24 h of REMSD for the non-social odor. RESULTS: Our findings demonstrated the occurrence of a strong association between the density of nigral TH-ir neurons and the olfactory discrimination capacity for both odorant stimuli. Specifically, the rotenone-induced decrease of these neurons tends to elicit reductions in the olfactory discrimination ability. CONCLUSIONS: These results are consistent with the participation of the nigrostriatal dopaminergic system mainly in the olfactory discrimination of a non-social odor, probably through the main olfactory pathway. Such involvement may have produce relevant impact in the preclinical abnormalities found in PD patients.

Cholinergic Oculomotor Nucleus Activity Is Induced by REM Sleep Deprivation Negatively Impacting on Cognition.

Several efforts have been made to understand the involvement of rapid eye movement (REM) sleep for cognitive processes. Consolidation or retention of recognition memories is severely disrupted by REM sleep deprivation (REMSD). In this regard, pedunculopontine tegmental nucleus (PPT) and other brainstem nuclei, such as pontine nucleus (Pn) and oculomotor nucleus (OCM), appear to be candidates to take part in this REM sleep circuitry with potential involvement in cognition. Therefore, the objective of this study was to investigate a possible association between the performance of Wistar rats in a declarative memory and PPT, Pn, and OCM activities after different periods of REMSD. We examined c-Fos and choline acetyltransferase (ChaT) expressions as indicators of neuronal activity as well as a familiarity-based memory test. The animals were distributed in groups: control, REMSD, and sleep rebound (REB). At the end of the different REMSD (24, 48, 72, and 96 h) and REB (24 h) time points, the rats were immediately tested in the object recognition test and then the brains were collected. Results indicated that OCM neurons presented an increased activity, due to ChaT-labeling associated with REMSD that negatively correlated (r = -0.32) with the cognitive performance. This suggests the existence of a cholinergic compensatory mechanism within the OCM during REMSD. We also showed that 24 h of REMSD impacted similarly in memory, compared to longer periods of REMSD. These data extend the notion that REM sleep is influenced by areas other than PPT, i.e., Pn and OCM, which could be key players in both sleep processes and cognition.

REM sleep deprivation promotes a dopaminergic influence in the striatal MT2 anxiolytic-like effects.

The aim of this study was to investigate the possible anxiolytic-like effects of striatal MT2 activation, and its counteraction induced by the selective blockade of this receptor. Furthermore, we analyzed this condition under the paradigm of rapid eye movement (REM) sleep deprivation (REMSD) and the animal model of Parkinson's disease (PD) induced by rotenone. Male Wistar rats were infused with intranigral rotenone (12 µg/µL), and 7 days later were subjected to 24 h of REMSD. Afterwards the rats underwent striatal micro-infusions of selective melatonin MT2 receptor agonist, 8-M-PDOT (10 µg/µL) or selective melatonin MT2 receptor antagonist, 4-P-PDOT (5 µg/µL) or vehicle. Subsequently, the animals were tested in the open-field (OP) and elevated plus maze (EPM) tests. Results indicated that the activation of MT2 receptors produced anxiolytic-like effects. In opposite, the MT2 blockade did not show an anxiogenic-like effect. Besides, REMSD induced anxiolytic-like effects similar to 8-M-PDOT. MT2 activation generated a prevalent locomotor increase compared to MT2 blockade in the context of REMSD. Together, these results suggest a striatal MT2 modulation associated to the REMSD-induced dopaminergic supersensitivity causing a possible dopaminergic influence in the MT2 anxiolytic-like effects in the intranigral rotenone model of PD.