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Comparison of the Melatonin Receptor Agonist Ramelteon and the Non-Benzodiazepine Hypnotic Zolpidem for Nocturia

Open Journal of Urology 2013年第8期3卷 293-298页

作者： Hideki Mukouyama Kimio Sugaya Saori Nishijima Hidekatsu Naka Misao Sakumoto Tomohiro Onaga Katsumi Kadekawa Katsuhiro Ashitomi Department of Urology Nanbu Tokushukai Hospital Okinawa Japan Department of Urology Okinawa Kyodo Hospital Okinawa Japan Nishizaki Hospital Okinawa Japan Sakumoto Urology and Dermatology Clinic Okinawa Japan Southern Knights’ laboratory LLP Okinawa Japan

To examine the efficacy of the melatonin receptor agonist ramelteon for nocturia, it was compared with zolpidem, a conventional non-benzodiazepine hypnotic. A total of 50 patients with nocturia (32 urinations/night) were enrolled. Subjects assigned odd numbers or even numbers were respectively prescribed 8 mg of ramelteon (n = 27;mean age: 75 years) or 5 mg of zolpidem (n = 23;mean age: 73 years) once a day before sleeping for 4 weeks. The daytime and nighttime frequencies of urination, as well as the results of global self-assessment by the patients, were compared between the two groups before and after 4 weeks of treatment. Both ramelteon and zolpidem caused a significant decrease of nocturia to about once per night after 4 weeks. The global self-assessment rating at 4 weeks was “good” or “fair” for more patients in the zolpidem group than in the ramelteon group, while the rating was “excellent” or “no change” for more patients in the ramelteon group. There were no serious adverse events in either group. Ramelteon was safe and effective for nocturia, achieving similar results to zolpidem. However, responders and non-responders to ramelteon were more clearly distinguished. Ramelteon might be effective for patients with sleep disturbance and nocturia because of low melatonin levels. Therefore, as diagnostic therapy for identification of nocturia caused by sleep disturbance and melatonin deficiency, ramelteon should be administered to patients who do not respond to alpha-1 antagonists and/or anticholinergic agents.

关键词： Ramelteon Nocturia Melatonin Zolpidem

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Autologous Transplantation for Parkinson's Disease Patients:Feasibility and Challenge

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Neuroscience Bulletin 2021年第7期37卷 1085-1086页

作者： Qi Zhang Yanlin Wang Yukai Wang Han Liu Huifang Sun Zhuoya Wang Changhe Shi Jing Yang Yuming Xu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhou 450052China State Key laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Department of National Stem Cell Resource Center Institute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China

Parkinson’s Disease(PD),second only to Alzheimer’s disease,is a neurodegenerative disease,most commonly occurring in people over the age of 65 years and is mostly caused by loss of dopamine neurons[1].Clinically,motor symptoms such as resting tremor,motor retardation,muscular rigidity,and disturbance of postural balance are the main symptoms,followed by non-motor symptoms such as cognitive impairment,autonomic nervous system dysfunction,depression,and sleep disorder[2].In 2016,>6.1 million people were affected with PD globally,2.4 times the number in *** large number of affected people,coupled with the high mortality and disability rates,has placed a great burden on society[3].Traditional treatment methods mainly include drugs and surgery and are supplemented by physical therapy.

关键词： drugs mortality Clinical

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Genetically Engineered Systems Revealed the Roles and Neuron Circuits of Basal Ganglia in sleep-wake Regulation

Genetically Engineered Systems Revealed the Roles and Neuron...

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中国神经科学学会第十二届全国学术会议

作者：黄志力 Department of Pharmacology School of Basic Medical Sciences State Key laboratory of Medical Neurobiology Institutes of Brain Science and Collaborative Innovation Center for Brain Science Shanghai Medical College Fudan University

The basal ganglia(BG) act as a cohesive functional unit that regulates motor function, habit formation, and reward/addictive behaviors. However, it is still not well understood how the BG maintains wakefulness and suppresses sleep to achieve all these fundamental functions until genetically engineered systems developed these years. Significant research efforts have recently been directed at developing genetic-molecular tools to achieve reversible and cell-type specific in vivo silencing or activation of neurons in behaving animals. Optogenetic tools can be used both to specifically activate or inhibit neurons of interest and identify functional synaptic connectivity between specific neuronal populations, both in vivo and in brain slices. Another recently developed system by Roth and colleagues permits the selective and "remote" manipulation(activation and silencing) of neuronal activity via all 3 major GPCR signaling pathways(G, G and G). These so-called "designer receptors exclusively activated by designer drugs"(DREADD) involve mutant GPCRs that do not respond to their endogenous ligands but are responsive to otherwise inert biological compounds. Recently, we demonstrated the essential roles and the neural pathways of the neurons expressing adenosine A2A receptors or dopamine D1 receptors in the different regions of BG for sleep-wake regulation using the genetically engineered systems including optogenetics and DREADD. We proposed a plausible model in which the caudate-putamen and the nucleus accumbens integrate behavioral processes with sleep/wakefulness through adenosine and dopamine receptors.

关键词： adeno-associated virus optogenetics DREADD basal ganglia sleep-wake regulation

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CIH-induced neurocognitive impairments are associated with hippocampal Ca2+ overload,apoptosis,and dephosphorylation of ERK1/2 and CREB that are mediated by overactivation of NMDARs

CIH-induced neurocognitive impairments are associated with h...

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中国睡眠研究会第九届学术年会

作者： Jing Wang Hong Ming Rui Chen Jing-mei Ju Wan-da Peng Guo-Xing Zhang Chun-feng Liu Department of Respiratory Medicine Sleeping CenterSecond Affiliated Hospital of Soochow University Department of Physiology Medical College of Soochow University laboratory of Aging and Nervous Diseases Institute of NeuroscienceSoochow University

Chronic intermittent hypoxia(CIH)is commonly seen in patients with obstructive sleep apnea,and has been hypothesized to underlie the neurocognitive dysfunction in these ***,its cellular and molecular mechanisms remain to be *** present study aimed to investigate,in a mouse CIH model,the role of NMDA receptor(NMDAR)activation in mediating the CIHinduced neurocognitive impairments,caspase expression and dysregulated Casignaling pathways

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sleep Promotion by 3-Hydroxy-4-Iminobutyric Acid in Walnut Diaphragma juglandis Fructus

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Research 2024年第2期6卷 613-627页

作者： Jian Ji Yongli Ye Lina Sheng Jiadi Sun Qianqian Hong Chang Liu Jun Ding Shuxiang Geng Deping Xu Yinzhi Zhang Xiulan Sun State Key laboratory of Food Science and Technology School of Food Science and TechnologyNational Engineering Research Center for Functional FoodSynergetic Innovation Center of Food Safety and Quality ControlJiangnan UniversityLihu Avenue 1800WuxiJiangsu 214100P.R.China College of Food Science and Pharmacy Xinjang Agricultural UniversityNo.311 Nongda Dong RoadUrumqiXinjangUygur Autonomous Region 830052P.R.China Department of Chemistry Wuhan UniversityWuhanHubei 430072P.R.China Yunnan Academy of Forestry and Grassland KunmingYunnan 650201P.R.China

Insufficient sleep can produce a multitude of deleterious repercussions on various domains of human ***,the walnut(Juglans mandshurica)confers numerous salutary biological activities pertaining to ***,the sedative and hypnotic capacities of walnut's functional constituents remain *** this investigation,we analyzed the sedative and hypnotic components of the walnut Diaphragma juglandis fructus and innovatively discovered a compound,defined as 3-hydroxy-4-iminobutyric acid(HIBA),which disrupts motor activity and enhances sleep duration by regulating the neurotransmitters(GABA,DA,etc.)within the brain and serum of ***,a metabolomics approach of the serum,basal ganglia,hypothalamus,and hippocampus as well as the gut microbiota was undertaken to unravel the underlying molecular mechanisms of sleep *** data reveal that HIBA can regulate the metabolism of basal ganglia(sphingolipids,acylcarnitines,etc.),possibly in relation to HIBA's influence on the gut microbiome(Muribaculum,Bacteroides,Lactobacillus,etc.).Therefore,we introduce a novel natural product,HIBA,and explicate the modulation of sleep promotion in mice based on the microbiota-gut-brain *** study contributes fresh insights toward natural product-based sleep research.

关键词： metabolism promotion insight

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Dopamine D2 receptor and sleep-wake regulation

Dopamine D2 receptor and sleep-wake regulation

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中国神经科学学会第十届全国学术会议

作者： Zhi-Li Huang Wei-Min Qu Department of Pharmacology Shanghai Medical CollegeFudan University State Key laboratory of Medical Neurobiology Shanghai Medical CollegeFudan University The Institute of Brain Science Shanghai Medical CollegeFudan University

Dopamine(DA) has been reported to regulate processes responsible for the generation of complex movements and emotions,cognition,reward processing,and drug ***,the role assigned to DA in sleep-wake regulation has been relatively *** main DA receptors(R) in the brain are DR and *** clarify the roles of DA receptors in the sleep-wake regulation,DR knock-out(KO) mice,selective gene deletion strategies based on focal RNA interference to silence the expression of DR,the human DR gene carried by AAV to focally rescue DR in DR KO mice,and pharmacological manipulation were *** found that the DR blockade could reduce the sleep latency and increase amounts of non-rapid eye movement(non-REM,NREM) *** is the most potent wake-promoting medicine for enhancing the extracellular DA level in the nucleus accumbens and the prefrontal cortex,and for increasing *** using DR KO mice and DR antagonist,we demonstrated that DR and DR are essential for the arousal effect of modafinil,with DR being the receptor of primary *** with wild-type(WT) mice,DR KO mice exhibited a significant decrease in *** the KO mice were subjected to a cage change,the latency to sleep in the KO mice decreased to half of the level for WT ***,focal RNA interference in WT mice and rescue technology for DR in the KO mice showed that DRs located in the core of NAc play more important role in promoting arousal and locomotion than other parts in the *** results indicate that DR plays an essential role in the maintenance of wakefulness.

关键词： dopamine D2 receptors sleep wakefulness AAV knockout

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Roles of the Basal Ganglia in sleep-wake Regulation

Roles of the Basal Ganglia in Sleep-wake Regulation

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2015年中国中西医结合学会时间生物医学专业委员会学术研讨暨换届会议

作者： Zhi-Li Huang Wei-Min Qu Fudan University School of Basic Medical SciencesDepartment of Pharmacology Fudan University Institutes of Brain Science and the Collaborative Innovation Center for Brain Science Fudan University State Key Laboratory of Medical Neurobiology

The basal ganglia(BG)are the largest structures in the forebrain and consist of four major nuclei,the striatum,globus pallidus,subthalamic nucleus,and substantia *** BG has been demonstrated to act as a cohesive functional unit that regulates motor function,habit formation,and reward/addictive behaviors,but the debate has only recently started on how the BG regulate sleep-wake behavior to achieve all these fundamental functions of the *** using neurotoxic lesion,pharmacological

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Manipulated overlapping reactivation of multiple memories promotes the abstraction of hidden gist

Manipulated overlapping reactivation of multiple memories pr...

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中国睡眠研究会第十五届全国学术年会

作者： Xiaoxia Zhao Po-han Chen Jie Chen Hongqiang Sun Peking University Sixth Hospital Peking University Institute of Mental Health NHC Key Laboratory of Mental Health (Peking University)National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)

Objective: sleep is considered to promote the gist abstraction on the basis of spontaneous memory *** speculated in the theory of ‘information overlap to abstract(iOtA)', ‘overlap' between reactivated memories, beyond reactivation, is crucial to gist *** so far, empirical research has not tested this theory by manipulating the factor of ‘overlap'.In the current study, ‘overlap' itself was manipulated by targeted memory reactivation(TMR), through simultaneously reactivating multiple memories containing hidden gist or not, to investigate the effect of overlapping reactivation on gist ***: This study had a factorial design with 2 factors with 2 levels respectively(overlap/non-overlap, TMR/no-TMR).Accordingly, 82 healthy college students(57 females, age range 19 ～ 25) were randomized into four *** learning of 16 pictures, paired with 4 auditory cues(4 pictures – 1 cue) according to the grouping, participants were given a 90-minute nap *** TMR cueing was conducted during N2 and slow wave sleep of *** in memory task was used to measure gist ***: Two-way ANOVA revealed a significant main effect of TMR on gist *** analyses showed that gist abstraction in overlapping reactivation group was significantly better than in control group, while gist abstraction in two non-overlapping groups were ***, gist abstraction was positively correlated with spindle density, as well as the strength and preferred phase of slow oscillation-spindle ***: The current study indicates that overlapping reactivation facilitates gist abstraction, spindle and and slow oscillationspindle coupling were correlated with this *** study thus provides empirical evidence for the iOtA theory.

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Non-alcoholic fatty liver disease and sleep disorders

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World Journal of Hepatology 2024年第3期16卷 304-315页

作者： Lu-Fang Bu Chong-Yu Xiong Jie-Yi Zhong Yan Xiong Dong-Ming Li Fen-Fang Hong Shu-Long Yang Department of Physiology Fuzhou Medical CollegeNanchang UniversityFuzhou 344000Jiangxi ProvinceChina Key laboratory of Chronic Diseases Fuzhou Medical UniversityFuzhou 344000Jiangxi ProvinceChina Technology Innovation Center of Chronic Disease Research in Fuzhou City Fuzhou Science and Technology BureauFuzhou 344000Jiangxi ProvinceChina Experimental Center of Pathogen Biology College of MedicineNanchang UniversityNanchang 330006Jiangxi ProvinceChina

Studies have shown that non-alcoholic fatty liver disease(NAFLD)may be associated with sleep *** order to explore the explicit relationship between the two,we systematically reviewed the effects of sleep disorders,especially obstructive sleep apnea(OSA),on the incidence of NAFLD,and analyzed the possible mechanisms after adjusting for confounding *** is independently associated with sleep *** sleep disorders may be the cause of the onset and aggravation of *** excessive or insufficient sleep duration,poor sleep quality,insomnia,sleep-wake disorders,and OSA may increase the incidence of *** that some research suggests a unidirectional causal link between the two,specifically,the onset of NAFLD is identified as a result of changes in sleep characteristics,and the reverse relationship does not hold ***,there is still a lack of specific research elucidating the reasons behind the higher risk of developing sleep disorders in individuals with *** research is needed to establish a clear relationship between NAFLD and sleep *** will lay the groundwork for earlier identification of potential patients,which is crucial for earlier monitoring,diagnosis,effective prevention,and treatment of NAFLD.

关键词： Non-alcoholic fatty liver disease sleep duration sleep quality sleep disorders Obstructive sleep apnea

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Synchrony between Ovarian Function &sleep in Polycystic Ovary Syndrome Patients

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Open Journal of Obstetrics and Gynecology 2014年第12期4卷 725-731页

作者： Farideh Zafari Zangeneh Mohammad Mehdi Naghizadeh Alireza Abdollahi Maryam Bagheri Department of Community Medicine Medical Faculty Fasa University of Medical Sciences Fasa Iran Pathology laboratory Vali-e-Asr Hospital Tehran University of Medical Sciences Tehran Iran Reproductive Health Research Center Tehran University of Medical Sciences Tehran Iran

Polycystic ovary syndrome (PCOS) is a complex, multifaceted, heterogeneous disorder, affecting 4% to 18% of reproductive-aged women and is associated with reproductive, metabolic and psychological dysfunction. In this study we determined the relationship between the time to sleep and serum levels of neurohormones in polycystic ovary syndrome (PCOS). Totally 77 PCO patients(case group) and 97 non-PCOS infertile women (control subjects) participated in this study between February 2012 and February 2013. A PSQI sleep questionnaire was completed by each patient in both groups. PSQI sleep questionnaire score and serum concentration of adrenaline, noradrenaline, melatonin, β-endorphin, cortisol and progesterone were compared in two groups. The results of the study indicate that serum levels of melatonin and β-endorphin were lower in women with PCOS. Serum level of stress hormones, adrenaline and noradrenaline were significantly correlated with patients’ sleep time in study group. Serum level of adrenaline in control group was significantly lower in women who wake up earlier in the morning. All hormones except for cortisol had no significant correlation with PSQI global score in both groups and also the people who sleep less than 8 hours had lower cortisol level. These data showed that changes in cortisol in PCO women were due to damage of disturbed sleep at night. Our preliminary work provided this study with new insight into the interactions between sleep-wake cycles in PCO women with specific sleep patterns.

关键词： Polycystic Ovary Syndrome (PCOS) sleep Stress Hormone β-Endorphin Melatonin

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