RESUMO
The relationship between mental disorders and sleep remains unclear. Two new studies show that the lateral habenula, a brain region associated with value-guided behavior, controls REM sleep and promotes emotional stability but also contributes to REM sleep disinhibition in depression.
Assuntos
Depressão , Sono REM , Sono REM/fisiologia , Humanos , Depressão/fisiopatologia , Animais , Habenula/fisiologia , Habenula/fisiopatologia , Saúde MentalRESUMO
Abstract.Background: There is growing evidence that understanding the role of sleep disturbance in bipolar disorder (BD) and major depressive disorder (MDD) is helpful when studying the high heterogeneity of patients across psychiatric disorders.Objective: The present study was designed to investigate the transdiagnostic role of sleep disturbance measured by polysomnography (PSG) in differentiating from MDD with BD.Methods: A total of 256 patients with MDD and 107 first-episode and never medicated patients with BD using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were recruited. All patients completed 1 night of PSG recording, and the changes in objective sleep structure parameters were determined by PSG analysis.Results: We showed that patients with MDD had statistically longer rapid eye movement (REM) latency, a higher percentage of stage N2 sleep, and lower percentages of stage N3 sleep and REM sleep than those with BD after controlling for confounding factors (all P < .05). Moreover, using the logistic regression analysis, we identified that REM latency was associated with BD diagnosis among the PSG sleep features. The cutoff value for PSG characteristics to differentiate BD from MDD was 261 in REM latency (sensitivity: 41.4% and specificity: 84.1%).Conclusions: Our findings suggest that PSG-measured sleep abnormalities, such as reduced REM latency, may be a diagnostic differentiating factor between MDD and BD, indicating their roles in identifying homogeneous transdiagnostic subtypes across psychiatric disorders.
Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Polissonografia , Humanos , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/fisiopatologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/fisiopatologia , Feminino , Masculino , Adulto , Diagnóstico Diferencial , Pessoa de Meia-Idade , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/fisiopatologia , Sono REM/fisiologia , Adulto Jovem , Fases do Sono/fisiologiaRESUMO
This study investigated the role of O-GlcNAc cycling in Alzheimer's disease-related changes in brain pathophysiology induced by chronic REM sleep deprivation (CSD) in mice. CSD increased amyloid beta (Aß) and p-Tau accumulation and impaired learning and memory (L/M) function. CSD decreased dendritic length and spine density. CSD also increased the intensity of postsynaptic density protein-95 (PSD-95) staining. All of these Alzheimer's disease (AD) pathogenic changes were effectively reversed through glucosamine (GlcN) treatment by enhancing O-GlcNAcylation. Interestingly, the lelvel of O-GlcNAcylated-Tau (O-Tau) exhibited an opposite trend compared to p-Tau, as it was elevated by CSD and suppressed by GlcN treatment. CSD increased neuroinflammation, as indicated by elevated levels of glial fibrillary acidic protein and IBA-1-positive glial cells in the brain, which were suppressed by GlcN treatment. CSD promoted the phosphorylation of GSK3ß and led to an upregulation in the expression of endoplasmic reticulum (ER) stress regulatory proteins and genes. These alterations were effectively suppressed by GlcN treatment. Minocycline not only suppressed neuroinflammation induced by CSD, but it also rescued the decrease in O-GlcNAc levels caused by CSD. Minocycline also reduced AD neuropathy without affecting CSD-induced ER stress. Notably, overexpressing O-GlcNAc transferase in the dentate gyrus region of the mouse brain rescued CSD-induced cognitive dysfunction, neuropathy, neuroinflammation, and ER stress responses. Collectively, our findings reveal that dysregulation of O-GlcNAc cycling underlies CSD-induced AD pathology and demonstrate that restoration of OGlcNAcylation protects against CSD-induced neurodegeneration.
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Doença de Alzheimer , Encéfalo , Privação do Sono , Animais , Camundongos , Privação do Sono/metabolismo , Privação do Sono/complicações , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Masculino , Camundongos Endogâmicos C57BL , Proteínas tau/metabolismo , Acetilglucosamina/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Sono REM/fisiologia , Peptídeos beta-Amiloides/metabolismoRESUMO
Brain function is vulnerable to the consequences of inadequate sleep, an adverse trend that is increasingly prevalent. The REM sleep phase has been implicated in coordinating various brain structures and is hypothesized to have potential links to brain variability. However, traditional imaging research have encountered challenges in attributing specific brain region activity to REM sleep, remained understudied at the whole-brain connectivity level. Through the spilt-night paradigm, distinct patterns of REM sleep phases were observed among the full-night sleep group (n = 36), the early-night deprivation group (n = 41), and the late-night deprivation group (n = 36). We employed connectome-based predictive modeling (CPM) to delineate the effects of REM sleep deprivation on the functional connectivity of the brain (REM connectome) during its resting state. The REM sleep-brain connectome was characterized by stronger connectivity within the default mode network (DMN) and between the DMN and visual networks, while fewer predictive edges were observed. Notably, connections such as those between the cingulo-opercular network (CON) and the auditory network, as well as between the subcortex and visual networks, also made significant contributions. These findings elucidate the neural signatures of REM sleep loss and reveal common connectivity patterns across individuals, validated at the group level.
Assuntos
Encéfalo , Conectoma , Imageamento por Ressonância Magnética , Privação do Sono , Sono REM , Humanos , Masculino , Privação do Sono/fisiopatologia , Privação do Sono/diagnóstico por imagem , Sono REM/fisiologia , Feminino , Adulto , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Adulto Jovem , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede de Modo Padrão/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologiaRESUMO
This study aimed to progress the understanding of idiopathic hypersomnia (IH) by assessing the moderating influence of individual characteristics, such as age, sex, and body mass index (BMI) on sleep architecture. In this retrospective study, 76 IH participants (38.1 ± 11.3 years; 40 women) underwent a clinical interview, an in-laboratory polysomnography with a maximal 9-h time in bed and a multiple sleep latency test (MSLT). They were compared to 106 healthy controls (38.1 ± 14.1 years; 60 women). Multiple regressions were used to assess moderating influence of age, sex, and BMI on sleep variables. We used correlations to assess whether sleep variables were associated with Epworth Sleepiness Scale scores and mean sleep onset latency on the MSLT in IH participants. Compared to controls, IH participants had shorter sleep latency (p = 0.002), longer total sleep time (p < 0.001), more time spent in N2 sleep (p = 0.008), and showed trends for a higher sleep efficiency (p = 0.023) and more time spent in rapid eye movement (REM) sleep (p = 0.022). No significant moderating influence of age, sex, or BMI was found. More severe self-reported sleepiness in IH patients was correlated with shorter REM sleep latency and less N1 sleep in terms of proportion and duration (ps < 0.01). This study shows that, when compared to healthy controls, patients with IH had no anomalies in their sleep architecture that can explain their excessive daytime sleepiness. Moreover, there is no moderating influence of age, sex, and BMI, suggesting that the absence of major group differences is relatively robust.
Assuntos
Índice de Massa Corporal , Hipersonia Idiopática , Polissonografia , Humanos , Feminino , Adulto , Masculino , Hipersonia Idiopática/fisiopatologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Etários , Sono/fisiologia , Sono REM/fisiologia , Fatores Sexuais , Adulto Jovem , Estudos de Casos e Controles , Fases do Sono/fisiologiaRESUMO
Rapid eye movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POAGAD2âTMN neurons) are crucial for the homeostatic regulation of REMs in mice. POAGAD2âTMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POAGAD2âTMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POAGAD2âTMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.
Assuntos
Neurônios GABAérgicos , Homeostase , Área Pré-Óptica , Sono REM , Animais , Área Pré-Óptica/fisiologia , Sono REM/fisiologia , Camundongos , Neurônios GABAérgicos/fisiologia , Masculino , Eletroencefalografia , Região Hipotalâmica Lateral/fisiologiaRESUMO
Idling brain activity has been proposed to facilitate inference, insight, and innovative problem-solving. However, it remains unclear how and when the idling brain can create novel ideas. Here, we show that cortical offline activity is both necessary and sufficient for building unlearned inferential knowledge from previously acquired information. In a transitive inference paradigm, male C57BL/6J mice gained the inference 1 day after, but not shortly after, complete training. Inhibiting the neuronal computations in the anterior cingulate cortex (ACC) during post-learning either non-rapid eye movement (NREM) or rapid eye movement (REM) sleep, but not wakefulness, disrupted the inference without affecting the learned knowledge. In vivo Ca2+ imaging suggests that NREM sleep organizes the scattered learned knowledge in a complete hierarchy, while REM sleep computes the inferential information from the organized hierarchy. Furthermore, after insufficient learning, artificial activation of medial entorhinal cortex-ACC dialog during only REM sleep created inferential knowledge. Collectively, our study provides a mechanistic insight on NREM and REM coordination in weaving inferential knowledge, thus highlighting the power of idling brain in cognitive flexibility.
Assuntos
Giro do Cíngulo , Aprendizagem , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal , Sono REM , Animais , Sono REM/fisiologia , Masculino , Córtex Pré-Frontal/fisiologia , Aprendizagem/fisiologia , Camundongos , Giro do Cíngulo/fisiologia , Vigília/fisiologia , Sono de Ondas Lentas/fisiologia , Conhecimento , Córtex Entorrinal/fisiologia , Neurônios/fisiologiaRESUMO
Sleep quality is an essential parameter of a healthy human life, while sleep disorders such as sleep apnea are abundant. In the investigation of sleep and its malfunction, the gold-standard is polysomnography, which utilizes an extensive range of variables for sleep stage classification. However, undergoing full polysomnography, which requires many sensors that are directly connected to the heaviness of the setup and the discomfort of sleep, brings a significant burden. In this study, sleep stage classification was performed using the single dimension of nasal pressure, dramatically decreasing the complexity of the process. In turn, such improvements could increase the much needed clinical applicability. Specifically, we propose a deep learning structure consisting of multi-kernel convolutional neural networks and bidirectional long short-term memory for sleep stage classification. Sleep stages of 25 healthy subjects were classified into 3-class (wake, rapid eye movement (REM), and non-REM) and 4-class (wake, REM, light, and deep sleep) based on nasal pressure. Following a leave-one-subject-out cross-validation, in the 3-class the accuracy was 0.704, the F1-score was 0.490, and the kappa value was 0.283 for the overall metrics. In the 4-class, the accuracy was 0.604, the F1-score was 0.349, and the kappa value was 0.217 for the overall metrics. This was higher than the four comparative models, including the class-wise F1-score. This result demonstrates the possibility of a sleep stage classification model only using easily applicable and highly practical nasal pressure recordings. This is also likely to be used with interventions that could help treat sleep-related diseases.
Assuntos
Algoritmos , Aprendizado Profundo , Redes Neurais de Computação , Polissonografia , Pressão , Fases do Sono , Humanos , Fases do Sono/fisiologia , Masculino , Adulto , Feminino , Adulto Jovem , Nariz/fisiologia , Voluntários Saudáveis , Sono REM/fisiologia , Vigília/fisiologiaRESUMO
OBJECTIVE: To compare the effect of stage 3 fragmentation and the paradoxical phase of night sleep on melatonin (MT) secretion, and to evaluate the effects of changes in autonomic balance and activation reactions that occur in the orthodox and paradoxical phases of sleep. MATERIAL AND METHODS: Fifteen healthy men participated in three sessions: with stage 3 fragmentation, with fragmentation of paradoxical sleep, and in a control experiment in which sleep was not disturbed. In each experiment, 7 saliva samples were collected in the evening, at night and in the morning and the MT content was determined. Heart rate variability was analyzed using an electrocardiogram and autonomic balance was assessed. RESULTS: Sleep fragmentation was accompanied by activation reactions and reduced the duration of stage 3 and paradoxical phase sleep by 50% and 51% in the corresponding sessions. Fragmentation of paradoxical sleep also led to an increase in the duration of night wakefulness. Sleep disturbances caused an increase in MT secretion in the second half of the night and in the morning, especially pronounced in sessions with fragmentation of paradoxical sleep, in which upon awakening MT was 1.8 times higher than in the control. Stage 3 fragmentation was accompanied by increased sympathetic activation, while fragmentation of paradoxical sleep did not cause autonomic shifts. The subjects were divided into 2 clusters: with high and low MT in night and morning saliva samples. In all sessions, subjects with high MT had 1.7-2 times longer duration of night wakefulness; in sessions with fragmentation, they had significantly more activations in the paradoxical phase of sleep. CONCLUSION: Night sleep disturbances cause an increase in MT secretion, especially pronounced during the fragmentation of the paradoxical phase. An increase in MT levels does not depend on changes in autonomic balance and is apparently associated with activation of the serotonergic system, which accompanies disturbances in the depth and continuity of sleep.
Assuntos
Melatonina , Saliva , Privação do Sono , Sono REM , Humanos , Melatonina/metabolismo , Masculino , Sono REM/fisiologia , Adulto , Saliva/metabolismo , Saliva/química , Privação do Sono/fisiopatologia , Privação do Sono/metabolismo , Sono de Ondas Lentas/fisiologia , Adulto Jovem , Frequência Cardíaca/fisiologia , Sistema Nervoso Autônomo/fisiopatologia , Sistema Nervoso Autônomo/metabolismo , Vigília/fisiologiaRESUMO
Out-of-body experiences (OBEs) are characterized by the subjective experience of being located outside the physical body. Little is known about the neurophysiology of spontaneous OBEs, which are often reported by healthy individuals as occurring during states of reduced vigilance, particularly in proximity to or during sleep (sleep-related OBEs). In this paper, we review the current state of research on sleep-related OBEs and hypothesize that maintaining consciousness during transitions from wakefulness to REM sleep (sleep-onset REM periods) may facilitate sleep-related OBEs. Based on this hypothesis, we propose a new conceptual model that potentially describes the relationship between OBEs and sleep states. The model sheds light on the phenomenological differences between sleep-related OBEs and similar states of consciousness, such as lucid dreaming (the realization of being in a dream state) and sleep paralysis (feeling paralyzed while falling asleep or waking up), and explores the potential polysomnographic features underlying sleep-related OBEs. Additionally, we apply the predictive coding framework and suggest a connecting link between sleep-related OBEs and OBEs reported during wakefulness.
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Sonhos , Paralisia do Sono , Humanos , Sonhos/fisiologia , Paralisia do Sono/fisiopatologia , Estado de Consciência/fisiologia , Vigília/fisiologia , Sono REM/fisiologiaAssuntos
Extinção Psicológica , Medo , Sono REM , Animais , Extinção Psicológica/fisiologia , Sono REM/fisiologia , CamundongosRESUMO
Rapid eye movement (REM) sleep has been hypothesized to promote emotional resilience, but any neuronal circuits mediating this have not been identified. We find that in mice, somatostatin (Som) neurons in the entopeduncular nucleus (EPSom)/internal globus pallidus are predominantly active during REM sleep. This unique REM activity is both necessary and sufficient for maintaining normal REM sleep. Inhibiting or exciting EPSom neurons reduced or increased REM sleep duration, respectively. Activation of the sole downstream target of EPSom neurons, Vglut2 cells in the lateral habenula (LHb), increased sleep via the ventral tegmental area (VTA). A simple chemogenetic scheme to periodically inhibit the LHb over 4 days selectively removed a significant amount of cumulative REM sleep. Chronic, but not acute, REM reduction correlated with mice becoming anxious and more sensitive to aversive stimuli. Therefore, we suggest that cumulative REM sleep, in part generated by the EP â LHb â VTA circuit identified here, could contribute to stabilizing reactions to habitual aversive stimuli.
Assuntos
Ansiedade , Sono REM , Animais , Camundongos , Sono REM/fisiologia , Ansiedade/fisiopatologia , Masculino , Área Tegmentar Ventral/fisiologia , Camundongos Endogâmicos C57BL , Gânglios da Base/fisiologia , Gânglios da Base/fisiopatologia , Neurônios/fisiologia , Núcleo Entopeduncular/fisiologia , Somatostatina/metabolismo , Habenula/fisiologia , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo , Proteína Vesicular 2 de Transporte de Glutamato/genéticaRESUMO
Psychiatric disorders with dysfunction of the lateral habenula (LHb) show sleep disturbance, especially a disinhibition of rapid eye movement (REM) sleep in major depression. However, the role of LHb in physiological sleep control and how LHb contributes to sleep disturbance in major depression remain elusive. Here, we found that functional manipulations of LHb glutamatergic neurons bidirectionally modulated both non-REM (NREM) sleep and REM sleep. Activity recording revealed heterogeneous activity patterns of LHb neurons across sleep/wakefulness cycles, but LHb neurons were preferentially active during REM sleep. Using an activity-dependent tagging method, we selectively labeled a population of REM sleep-active LHb neurons and demonstrated that these neurons specifically promoted REM sleep. Neural circuit studies showed that LHb neurons regulated REM sleep via projections to the ventral tegmental area but not to the rostromedial tegmental nucleus. Furthermore, we found that the increased REM sleep in a depression mouse model was associated with a potentiation of REM sleep-active LHb neurons, including an increased proportion, elevated spike firing, and altered activity mode. Importantly, inhibition of REM sleep-active LHb neurons not only attenuated the increased REM sleep but also alleviated depressive-like behaviors in a depression mouse model. Thus, our results demonstrated that REM sleep-active LHb neurons selectively promoted REM sleep, and a potentiation of these neurons contributed to depression-associated sleep disturbance.
Assuntos
Habenula , Neurônios , Sono REM , Animais , Habenula/fisiologia , Habenula/fisiopatologia , Sono REM/fisiologia , Camundongos , Neurônios/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Transtornos do Sono-Vigília/fisiopatologia , Depressão/fisiopatologiaRESUMO
Drug addiction may result in sleep problems. Importantly, sleep deprivation (SD) is known as an important risk factor for relapse to drug abuse as SD mimics the effects of psychostimulants on dopamine system of the brain. Moreover, aging may affect sleep and drug addiction. This study, therefore, set out to assess the effects of methamphetamine (METH) and REM sleep deprivation (RSD) on locomotor activity, anxiety-like behavior and spatial memory in adult and adolescent rats. Adult and adolescent male Wistar rats received a neurotoxic METH regimen; four subcutaneous injections of 6 mg/kg, at 2 h intervals. Five days later, the animals underwent a 48-h RSD episode using the multiple platforms method. They were then examined using the open field (OF), elevated plus maze (EPM) and Y-maze tasks. We found that the METH and RSD paradigms showed synergistic effects to increase locomotion and risk-taking behavior in both adult and adolescent animals, while only adolescent rats revealed RSD-induced anxiety-like behavior. Moreover, adolescent animals revealed greater sensitization for vertical activity following METH plus RSD episode. In addition, METH and RSD paradigms revealed synergistic effects to impair spatial working memory, but neither METH nor RSD alone affected performance of animals in the Y-maze task. Our findings may indicate that there are important relationships between METH and RSD to induce hyperlocomotion, risk-taking behavior and spatial memory impairment, particularly in adolescent animals. Moreover, it seems that adolescent rats may be more susceptible to anxiety-like behavior and hyperlocomotion than adults.
Assuntos
Ansiedade , Estimulantes do Sistema Nervoso Central , Aprendizagem em Labirinto , Metanfetamina , Ratos Wistar , Privação do Sono , Animais , Metanfetamina/farmacologia , Masculino , Estimulantes do Sistema Nervoso Central/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Memória Espacial/efeitos dos fármacos , Memória Espacial/fisiologia , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Sono REM/efeitos dos fármacos , Sono REM/fisiologia , Atividade Motora/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Envelhecimento/fisiologia , Envelhecimento/efeitos dos fármacosRESUMO
OBJECTIVE: Rapid eye movement (REM)-dependent obstructive sleep apnea syndrome (OSAS) is a specific subtype of OSAS having some phenotypic characteristics like a preference for a younger age, female gender, and milder severity. Such favorable features could make it possible to consider an overall benign course for this phenotype. However, accumulating data introduced its association with several cardiometabolic and vascular disorders recently. The primary objective of this study was to address the disease from the inflammation perspective and evaluate the potential inflammatory status in this variant via two accessible blood parameters: platelet distribution width (PDW) and systemic immune-inflammation index (SII). The secondary aim was to investigate whether this status, together with other disease characteristics, demonstrates consistency under different definitions of REM-dependent OSAS published previously. PATIENTS AND METHODS: The medical records of 35 patients with mild-to-moderate REM-dependent OSAS, 35 age- and sex-matched patients with REM-independent OSAS, and 25 non-OSA controls were retrospectively analyzed. Baseline features, polysomnographic characteristics, PDW, and SII were compared between the groups. Secondly, the analyses were repeated using different definitions of REM-dependent OSAS. Bivariate analyses were performed, and a multiple stepwise regression model was applied to adjust for body mass index (BMI) and cardiovascular risk (CVR) factors. RESULTS: Mean PDW and SII were increased in patients with REM-dependent OSAS as compared to non-OSA controls (p = .022 and .029). The significance remained stable after adjustment for BMI and CVRs and was consistent according to different definitions. The Comparison of patients with REM-independent OSAS and non-OSA controls, as well as the two different subtypes of OSAS, did not yield significance. CONCLUSION: Based on the current findings, patients with REM-dependent OSAS appear to be susceptible to inflammation and should be carefully monitored for the negative consequences of that issue. To our knowledge, this study is the first to evaluate SII and PDW in REM-dependent OSAS.
Assuntos
Inflamação , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Inflamação/sangue , Inflamação/fisiopatologia , Adulto , Estudos Retrospectivos , Sono REM/fisiologia , Polissonografia , Idoso , Índice de Massa CorporalRESUMO
Rapid eye movement sleep (REMS) is increasingly suggested as a discriminant sleep state for subtle signs of age-related neurodegeneration. While REMS expression is under strong circadian control and circadian dysregulation increases with age, the association between brain aging and circadian REMS regulation has not yet been assessed. Here, we measure the circadian amplitude of REMS through a 40-h in-lab multiple nap protocol in controlled laboratory conditions, and brain microstructural integrity with quantitative multi-parameter mapping (MPM) imaging in 86 older individuals. We show that reduced circadian REMS amplitude is related to lower magnetization transfer saturation (MTsat), longitudinal relaxation rate (R1) and effective transverse relaxation rate (R2*) values in several white matter regions mostly located around the lateral ventricles, and with lower R1 values in grey matter clusters encompassing the hippocampus, parahippocampus, thalamus and hypothalamus. Our results further highlight the importance of considering circadian regulation for understanding the association between sleep and brain structure in older individuals.
Assuntos
Encéfalo , Ritmo Circadiano , Imageamento por Ressonância Magnética , Sono REM , Humanos , Idoso , Masculino , Feminino , Sono REM/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Pessoa de Meia-Idade , Envelhecimento , Idoso de 80 Anos ou maisRESUMO
Many behaviors require the coordinated actions of somatic and autonomic functions. However, the underlying mechanisms remain elusive. By opto-stimulating different populations of descending spinal projecting neurons (SPNs) in anesthetized mice, we show that stimulation of excitatory SPNs in the rostral ventromedial medulla (rVMM) resulted in a simultaneous increase in somatomotor and sympathetic activities. Conversely, opto-stimulation of rVMM inhibitory SPNs decreased both activities. Anatomically, these SPNs innervate both sympathetic preganglionic neurons and motor-related regions in the spinal cord. Fiber-photometry recording indicated that the activities of rVMM SPNs correlate with different levels of muscle and sympathetic tone during distinct arousal states. Inhibiting rVMM excitatory SPNs reduced basal muscle and sympathetic tone, impairing locomotion initiation and high-speed performance. In contrast, silencing the inhibitory population abolished muscle atonia and sympathetic hypoactivity during rapid eye movement (REM) sleep. Together, these results identify rVMM SPNs as descending spinal projecting pathways controlling the tone of both the somatomotor and sympathetic systems.
Assuntos
Bulbo , Medula Espinal , Sistema Nervoso Simpático , Animais , Masculino , Camundongos , Locomoção/fisiologia , Bulbo/fisiologia , Camundongos Endogâmicos C57BL , Neurônios Motores/fisiologia , Neurônios/fisiologia , Sono REM/fisiologia , Medula Espinal/fisiologia , Sistema Nervoso Simpático/fisiologia , Comportamento Animal , Contagem de Células , Músculo EsqueléticoRESUMO
Huntington's disease (HD) is a rare neurodegenerative disorder with a distinct phenotype, including involuntary movements, cognitive decline, and behavioral disturbances. Sleep disorder include insomnia, increased sleep onset latency, decrease in total sleep time with frequent nocturnal awakenings and excessive daytime sleepiness. Increased sleep motor activities and abnormal nocturnal agitation have been increasingly recognized as an important component affecting negatively the sleep quality. Here, we report a case of an intensification of diurnal choreic movement during the night, notably during REM-sleep in a patient with manifest HD. This case highlights the diversity of nocturnal sleep motor disorders encountered in HD.
Assuntos
Doença de Huntington , Humanos , Doença de Huntington/complicações , Doença de Huntington/fisiopatologia , Masculino , Pessoa de Meia-Idade , Feminino , Transtornos do Sono-Vigília/fisiopatologia , Transtornos do Sono-Vigília/etiologia , Sono REM/fisiologia , Polissonografia , Sono/fisiologiaRESUMO
BACKGROUND: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. METHODS: Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. RESULTS: Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. CONCLUSION: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.