Thesis (D. Psych.)--Victoria University of Technology, 2005. / Includes bibliographical references.

Chen, Yu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 75-78). / Abstracts in English and Chinese. / Isolation and Identification of Differentially Expressed Protein in Serum of Patients with Sleep Disorders --- p.I / Abstract --- p.IV / 論文摘要 --- p.VII / Acknowledgements --- p.IX / Table of Contents --- p.X / List of Figures --- p.XII / List of Tables --- p.XII / List of Abbreviations --- p.XIII / Chapter Chapter 1: --- Introduction --- p.2 / Chapter 1.1 --- Definition of narcolepsy --- p.2 / Chapter 1.2 --- Symptoms of narcolepsy --- p.2 / Chapter 1.2.1 --- Excessive Daytime Sleepiness (EDS) --- p.2 / Chapter 1.2.2 --- Cataplexy --- p.2 / Chapter 1.2.3 --- Associated features --- p.3 / Chapter 1.3 --- Prevalence of narcolepsy --- p.4 / Chapter 1.4 --- Pathophysiology and molecular genetics of narcolepsy --- p.7 / Chapter 1.4.1 --- Pathophysiology of narcolepsy --- p.7 / Chapter 1.4.2 --- Molecular genetics research --- p.8 / Chapter 1.5 --- Diagnostic criteria for narcolepsy --- p.12 / Chapter 1.6 --- Treatment of narcolepsy --- p.16 / Chapter 1.7 --- The Burden of narcolepsy --- p.18 / Chapter 1.8 --- Human blood serum/plasma --- p.19 / Chapter 1.9 --- Cerebrospinal fluid (CSF) --- p.23 / Chapter 1.10 --- Aims of study --- p.26 / Chapter Chapter 2: --- Materials and Methods --- p.28 / Chapter 2.1 --- Participants and measurements --- p.28 / Chapter 2.1.1 --- Participants --- p.28 / Chapter 2.1.2 --- Diagnosis measurements --- p.28 / Chapter 2.2 --- "Serum extraction, albumin and IgG depletion" --- p.30 / Chapter 2.2.1 --- Albumin and IgG Depletion Kit --- p.30 / Chapter 2.2.2 --- Chemicals and reagents --- p.30 / Chapter 2.2.3 --- Preparation of solutions --- p.30 / Chapter 2.2.4 --- Procedure --- p.30 / Chapter 2.3 --- Reversed Phase High Performance Liquid Chromatography (RP-HPLC) --- p.32 / Chapter 2.3.1 --- RP-HPLC method --- p.32 / Chapter 2.3.2 --- Chemicals and reagents --- p.33 / Chapter 2.3.3 --- Preparation of mobile phases --- p.33 / Chapter 2.3.4 --- Procedure --- p.33 / Chapter 2.4 --- MALDI-TOF/TOF Mass Spectrometry --- p.35 / Chapter 2.4.1 --- Chemicals and reagents --- p.35 / Chapter 2.4.2 --- Preparation of solutions --- p.35 / Chapter 2.4.3 --- Procedure --- p.35 / Chapter 2.5 --- SDS-PAGE and double staining --- p.37 / Chapter 2.5.1 --- Chemicals and reagents --- p.37 / Chapter 2.5.2 --- Preparation of solutions --- p.37 / Chapter 2.5.3 --- Procedure --- p.39 / Chapter 2.6 --- N-terminal amino acid analysis --- p.42 / Chapter 2.6.1 --- Procedure --- p.42 / Chapter 2.6.2 --- Sequence analysis --- p.42 / Chapter 2.7 --- CSF analysis --- p.43 / Chapter Chapter 3: --- Results --- p.45 / Chapter 3.1 --- Albumin and IgG depletion of human serum samples --- p.45 / Chapter 3.2 --- Peak identification --- p.47 / Chapter 3.2.1 --- Peak identification on HPLC profiles --- p.47 / Chapter 3.2.2 --- Statistical results --- p.51 / Chapter 3.2.3 --- Family cases analysis --- p.54 / Chapter 3.3 --- MALDI-TOF/TOF Mass Spectrometry --- p.56 / Chapter 3.4 --- SDS-PAGE and double staining --- p.58 / Chapter 3.5 --- Protein sequence analysis --- p.60 / Chapter 3.6 --- Cerebrospinal fluid (CSF) analysis --- p.62 / Chapter Chapter 4: --- Discussion --- p.65 / Chapter 4.1 --- RP-HPLC methods --- p.65 / Chapter 4.2 --- The detected peptide fragment and Hlark --- p.66 / Chapter 4.2.1 --- "Human Lark protein (Hlark, hlark)" --- p.66 / Chapter 4.2.2 --- Circadian clocks --- p.67 / Chapter 4.2.3 --- "Hlark, circadian rhythm and narcolepsy" --- p.71 / Chapter 4.3 --- Familial and genetic analysis --- p.72 / Chapter 4.4 --- Clinical implications --- p.73 / Chapter 4.5 --- Conclusion --- p.74 / References --- p.75

Conclusion. A much higher percentage of narcolepsy and narcolepsy spectrum disorders was identified in our family study than previous reports. Most of the cases were asymptomatic. The shortened MSL and SOREMPs should be regarded as endophenotypes of narcolepsy. Nocturnal sleep variability was found to be associated with a diagnosis of narcolepsy, daytime shortened MSL and SOREMPs among the relatives. Our data was more concordant with a hypothesis of state boundary control/state instability for narcolepsy. Further molecular genotyping with the incorporation of endophenotype concept should be planned. / Introduction. Most familial studies on narcolepsy lacked detailed face-to-face clinical interviews and objective polysomnogram (PSG) and daytime multiple sleep latency test (MSLT) measurements. Our preliminary family study found one relative (2.9%) with narcolepsy and about 30% of the relatives fulfilled the criteria of narcolepsy spectrum disorder (shortened mean sleep latency [MSL] and/or the presence of sleep onset REM periods [SOREMPs]) The aim of this study was to further explore the familial aggregation and transmission pattern in a larger sample of Hong Kong Chinese narcolepsy, all based on detailed face-to-face interviews and objective measurements. / Methods. Thirty-four narcolepsy (with/without cataplexy) patients, one hundred and two relatives of these probands and forty-eight healthy controls were included in the study. All probands, relatives and controls underwent an overnight standard nocturnal PSG and a daytime MSLT on the following day. In addition, each subject also had a detailed clinical interview and completed sleep questionnaires. HLA DQB1*0602 genotyping was performed for 32 probands, 94 relatives and 30 controls. / Results. Seven (6.9%) relatives were diagnosed as narcolepsy with cataplexy and 9 (8.8%) relatives were diagnosed as narcolepsy without cataplexy. 39 (38.2%) had narcolepsy spectrum disorder and 47 (46.1%) were considered to be normal. A very strong familial aggregation of narcolepsy, narcolepsy spectrum disorder with associated features of shortened MSL (≤8min) and multiple SOREMPs were found in relatives, but not for sleep related hallucinations and sleep paralysis. Cataplexy seemed to breed true with exclusive but a low percentage of occurrence in the relatives of cataplectic-narcoleptic probands when comparing to the non-cataplectic probands (9% v.s. 0%). A close correlation of HLA-DQB1*0602 with cataplexy was found in both probands and their relatives. The narcoleptic relatives had an excess winter-birth when compared to normal relatives. On the other hand, the first-degree relatives of probands born in other seasons rather than winter had a shorter sleep latency in nocturnal sleep and a shorter mean sleep latency in MSLT. Our data suggested a Mendelian recessive model and multiplicative model for the inheritance of narcolepsy and a Mendelian dominant model for narcolepsy spectrum. Subjective questionnaires were unable in differentiating relatives with narcolepsy spectrum disorder from others. Relatives with narcolepsy reported a high rate of irregular sleep-wake patterns with both variable bedtime and nocturnal sleep duration. This nocturnal sleep variability correlated with daytime shortened MSL and SOREMPs among the relatives. In addition, shortened MSL and SOREMPs should be considered as endophenotypes of narcolepsy as they are the intermediate phenotypes that are heritable, state independent, associated with disease in the population and co-segregated with the disease within families. / Chen, Lei. / Adviser: Wing Yun Kwok. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3775. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 59-70). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Introduction: Cataplexy - the sudden involuntary loss of skeletal muscle tone – is a defining feature of narcolepsy. The current study aimed to determine if cataplexy is influenced by direct manipulation of REM sleep circuitry. We did this by pharmacogenetically inhibiting the REM sleep center, subcoeruleus (Sub-C). Methods: Inhibitory DREADD (hM4D-Gi) was bilaterally targeted to the Sub-C in hypocretin knockout mice (n=7). Intraperitoneal administration of clozapine-n-oxide was used to inhibit Sub-C cells expressing hM4D-Gi. Electrophysiological and behavioral criteria were used to characterize cataplexy and REM sleep. Results: Sub-C inhibition increased REM sleep and cataplexy amounts (p<0.05). Sub-C inhibition increased time spent in cataplexy amounts by increasing the number of cataplexy attacks (p<0.05). This intervention triggered increases in basal muscle tone during REM sleep, but had negligible effects on muscle tone during cataplexy (p>0.05). Conclusion: Pharmacogenetic manipulation of the Sub-C suggest that REM sleep and cataplexy are mediate by similar neural mechanism.

Introduction: Cataplexy - the sudden involuntary loss of skeletal muscle tone – is a defining feature of narcolepsy. The current study aimed to determine if cataplexy is influenced by direct manipulation of REM sleep circuitry. We did this by pharmacogenetically inhibiting the REM sleep center, subcoeruleus (Sub-C). Methods: Inhibitory DREADD (hM4D-Gi) was bilaterally targeted to the Sub-C in hypocretin knockout mice (n=7). Intraperitoneal administration of clozapine-n-oxide was used to inhibit Sub-C cells expressing hM4D-Gi. Electrophysiological and behavioral criteria were used to characterize cataplexy and REM sleep. Results: Sub-C inhibition increased REM sleep and cataplexy amounts (p<0.05). Sub-C inhibition increased time spent in cataplexy amounts by increasing the number of cataplexy attacks (p<0.05). This intervention triggered increases in basal muscle tone during REM sleep, but had negligible effects on muscle tone during cataplexy (p>0.05). Conclusion: Pharmacogenetic manipulation of the Sub-C suggest that REM sleep and cataplexy are mediate by similar neural mechanism.

Thesis (Ph.D.) - Carleton University, 2002. / Includes bibliographical references (p. 152-169). Also available in electronic format on the Internet.

No description available.

Narkolepsi är en relativt okänd sjukdom som kan ha stor påverkan på det dagliga livet. Sjukdomen kännetecknas av symtomen överdriven dagtrötthet (EDS), kataplexi (muskelsvaghet), sömnparalys samt hallucinationer. Symtomen upplevs ofta som problematiska och blir lätt missförstådda. Dagliga aktiviteter så som arbete, skolgång, bilkörning och sociala aktiviteter kan påverkas negativt. För att uppmärksamma hur narkolepsi upplevs av drabbade människor och deras anhöriga samt hur deras vardag påverkas behövs mer kunskap kring ämnet. Studiens syfte var att belysa hur människor med narkolepsi och deras anhöriga upplever sjukdomen. Metoden som användes var en allmän litteraturstudie och resultatet baserades på 14 vetenskapliga artiklar. Begränsningar i vardagen och Sjukdomsrelaterad påverkan utgjorde resultatets två huvudteman. I resultatet framkom att narkolepsi orsakar svårigheter för både de människor som drabbats av sjukdomen och deras anhöriga. Barn och ungdomars skolgång samt vuxnas arbetssituation påverkades negativt. Även sociala relationer till både familj och vänner kunde försämras. Sjuksköterskan kan utgöra ett stöd för både människor som drabbats av narkolepsi och deras anhöriga och genom kunskap, omtanke och ansvar kan mening i situationen uppnås. Aktuell forskning är otillräcklig och mer kunskap krävs för att människor drabbade av narkolepsi och deras anhöriga ska få en ljusare vardag. / Narcolepsy is a relatively unknown disease that can have a major impact on daily life. The disease is characterized by symptoms of excessive daytime sleepiness (EDS), cataplexy (muscle weakness), sleep paralysis and hallucinations. The symptoms are easily misunderstood and daily activities such as work, school, driving and social activities may be adversely affected. To observe how narcolepsy is experienced by affected people and their families and how their everyday lives are affected, more knowledge is needed on the subject. The study’s purpose was to identify how people with narcolepsy and their families are experiencing the disease. The method used was a literature overview and the results were based on 14 scientific articles. Limitations in everyday life and Disease-related impacts were the two main themes. The result showed that narcolepsy is causing difficulties. Children and young peoples’ schooling, adults’ job situations and social relationships are negatively affected. The nurse can be a support for both the people who suffer from narcolepsy and their families and by knowledge, consideration and responsibility the nurse can accomplish meaning in the situation. Current research is lacking and more knowledge is required to bring those who sufferers from narcolepsy and their families a brighter everyday life.

Narcolepsia é uma condição neurológica crônica, o principal sintoma é a sonolência diurna excessiva, associada a cataplexia, a paralisia do sono e as alucinações hipnagógicas. Paciente com narcolepsia apresenta dificuldade em manter a atenção e vigilância nas tarefas rotineiras e monótonas, com riscos de acidentes acarretando um sério prejuízo e impacto social nas suas relações de trabalho e sócio-familiares e na percepção da qualidade de vida.Foram avaliados 40 pacientes ( 28 mulheres e 12 homens) com idade média de 42 anos. O presente trabalho teve como objetivo: a) avaliar a percepção da QV em pacientes com narcolepsia b) Avaliar a percepção do impacto social. Este estudo demonstrou que: 1) A narcolepsia acarreta comprometimento na QV dos pacientes, com prejuízo das funções físicas e emocionais, interferindo nas condições de trabalho e dinâmica familiar; 2) A narcolepsia produz um impacto social em várias esferas da vida do pacientes, comprometendo atividades instrumentais da vida diária e a situação de trabalho / Narcolepsy is a chronic neurological condition, whose main symptom is excessive daytime sleepiness, associate the cataplexy, the hypnogogic hallucinations and sleep paralysis. The patient with narcolepsy presents difficulty in keeping the attention and monitoring in the routine and monotonous tasks, with risks of accidents, causing a serious prejudice and social impact its partner-familiar, relations of work and in the perception of the quality of life. The present work had as objective: ) to evaluate the perception of the quality of life in patients with narcolepsy b) To evaluate the perception of the social impact. This study it demonstrated that: 1) The narcolepsy compromises the quality of life of the patients, with prejudice of the physical and emotional functions, intervening with the conditions of work and familiar dynamics; 2) The narcolepsy produces a social impact in some areas of the life of the patients, compromising instrumental activities of the daily life and the situation of work

Narcolepsy is a neurological disorder characterized by a person’s inability to regulate sleep-wake cycles. Excessive daytime sleepiness and cataplexy are prominent symptoms of narcolepsy. Cataplexy is partial to full body muscle atonia usually brought on by the person with narcolepsy experiencing a positive emotion. Some features of cataplexy resemble those of REM sleep, including similar brain activity and muscle atonia. The neuronal circuit that produces cataplexy has yet to be determined. The similarities between REM sleep and cataplexy support the hypothesis that cataplexy is the result of the REM atonia pathways being activated. An emotion processing region, the central amygdala (CeA), projects to known REM regulatory regions and plays a role in cataplexy. GABAergic neurons of the CeA are sufficient and necessary to trigger cataplexy in mice and project to brainstem regions that regulate muscle tone. Cataplexy is often triggered in a social setting, such as when seeing an old friend or telling a joke. Oxytocin (OT) is involved in many social behaviors, making it a viable link between social stimuli and cataplexy. We hypothesized that oxytocin receptor (OTR) neurons of the CeA, a sub-population of GABAergic neurons, promote emotionally-triggered cataplexy. To determine the social phenotype of the narcolepsy mouse model, the orexin knock-out (OXKO) mouse, we used established behavioral assays of social interaction and social memory. To determine if social reunification influenced the amount of cataplexy, group-housed OXKO mice were isolated for a short time and reunited with their littermates. To determine if OTR neurons of the CeA were sufficient and necessary to promote socially-triggered cataplexy, we used chemogenetic technology known as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to selectively activate or inhibit these neurons. We injected adeno-associated viral vectors coding for either the excitatory hM3 Cre-dependent DREADD or the inhibitory hM4 Cre-dependent DREADD into the CeA of orexin knock-out mice crossed with OTR-Cre mice, allowing for expression of the DREADD exclusively in the OTR neurons of the CeA. After injection with either saline or clozapine-N-oxide (CNO) we put the mice through a behavioral assay to see if emotionally-triggered cataplexy increased or decreased following the activation or inhibition of OTR neurons of the CeA. The behavioral assays showed that acute social interactions in OXKO is normal, however they do have a social memory impairment. In addition, reunification promotes cataplexy in most OXKO mice. With the chemogenetic experiments, our number of mice is too low to report if OTR neurons of the CeA are sufficient and/or necessary for cataplexy at this time. / 2020-07-03T00:00:00Z