Relationship between CSF hypocretin levels and hypocretin neuronal loss

Gerashchenko, Dmitry; Murillo-Rodrı́guez, Eric; Li, Gang; Xu, Man; Hallett, Laura; Nishino, Seiji; Mignot, Emmanuel; Shiromani, Priyattam J.

doi:10.1016/s0014-4886(03)00388-1

Cited by 144 publications

(71 citation statements)

References 25 publications

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“…This inconsistency is probably due to the fact that orexin-A level can be partially compensated by the remaining neurons when exposed to the stress of degeneration. After lesioning orexin neurons with neurotoxin orexin-saporin, it was reported that the loss of 73% neurons only caused a 50% reduction in the orexin level of CSF [15] , suggesting that the loss of orexin neurons precedes the alteration of orexin level in CSF. This has also been verified in a postmortem study in PD patients, which shows that the 50% loss of orexin neurons is accompanied by its 25% lowered CSF level [8] .…”

Section: Discussionmentioning

confidence: 99%

Progressive changes of orexin system in a rat model of 6-hydroxydopamineinduced Parkinson’s disease

Cui

Li²,

Jin³

et al. 2010

Neurosci. Bull.

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Objective Sleep disturbance, which is characterized by excessive daytime sleepiness and sleep attacks, is frequently observed in patients with Parkinson's disease (PD). Loss of orexin neurons in hypothalamus and the resultant decreased level of orexin in cerebrospinal fluid (CSF) found in narcolepsy patients may also play an essential role in the pathogenesis of sleep disturbance. The present study aimed to investigate the possible changes in the orexin system during PD progression. Methods After the establishment of a rat PD model by injecting 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, the numbers of orexin-A-and tyrosine hydroxylase (TH)-positive neurons, and the levels of orexin-A fibers and orexin-A in CSF were examined by immunohistochemistry and ELISA assay, respectively. Results Compared to the TH-containing neurons that exhibited fast degeneration in response to 6-OHDA, orexin-A-containing neurons were less sensitive to 6-OHDA. The number of orexin-A-positive neurons began to decrease at day 21 after operation, and at day 49, it decreased by 30% of the initial level. The orexin-A level in CSF of PD rats did not show any obvious fluctuations compared to the control, and there was no obvious reduction in the density of orexin-A-positive fibers in brain areas such as tuberomammillary nucleus. Conclusion These results reveal for the first time the dynamic changes of orexin system during the progression of PD. This may provide valuable information for drug development to reverse the loss of orexin neurons and sleep disturbance in PD patients.

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Section: Discussionmentioning

confidence: 99%

Progressive changes of orexin system in a rat model of 6-hydroxydopamineinduced Parkinson’s disease

Cui

Li²,

Jin³

et al. 2010

Neurosci. Bull.

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“…[75][76][77][78] Hypocretin-1 levels below 110pg/ mL are highly specific (99%) and sensitive (87-89%) for narcolepsy cases with cataplexy, but not sensitive for cases without cataplexy (Table 1). However, because 16% of the cases of narcolepsy without cataplexy are accompanied by lumbar hypocretin-1 levels above 110pg/mL, this finding does not exclude the diagnosis of narcolepsy without cataplexy.…”

Section: 72mentioning

confidence: 99%

Diretrizes brasileiras para o diagnóstico de narcolepsia

Alóe

Alves

Araújo

et al. 2010

Rev. Bras. Psiquiatr.

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Este artigo relata as conclusões da reunião de consenso com médicos especialistas sobre diagnóstico de narcolepsia baseada na revisão dos artigos sobre narcolepsia listados no Medline entre 1980 e 2010. A narcolepsia é uma doença crônica de início entre a primeira e segunda décadas de vida do indivíduo. Os sintomas essenciais são cataplexia e sonolência excessiva. A cataplexia é definida como episódios súbitos, recorrentes e reversíveis de fraqueza da musculatura esquelética desencadeados por situações de conteúdo emocional. Os sintomas acessórios são alucinações hipnagógicas, paralisia do sono e sono fragmentado. Critérios de diagnóstico clínico de acordo com a Classificação Internacional dos Transtornos do Sono são de sonolência excessiva e cataplexia. Recomenda-se a realização de polissonografia seguida do teste de latência múltipla do sono em um laboratório de sono para confirmação e diagnóstico de comorbidades. Quando não houver cataplexia, deve haver duas ou mais sonecas com sono REM no teste de latência múltipla do sono. Tipagem HLA-DQB1*0602 positiva com níveis de hipocretina-1 abaixo de 110pg/mL devem estar presentes para o diagnóstico de narcolepsia sem cataplexia e sem sonecas com sono REM.

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“…However, Petersen et al reported an approximate 27 % loss of hypocretin neurons in human HD [8]. We think that this discrepancy may be due to quantitative effects: Gerashchenko and colleagues [10] found that an average loss of 14 % of rodent hypocretin neurons was not followed by a decrease of CSF hypocretin levels. An average loss of 73 %, however, was associated with a significant 50 % decline in CSF hypocretin levels.…”

mentioning

confidence: 91%