HPLC analysis of CSF hypocretin-1 in type 1 and 2 narcolepsy
العنوان: | HPLC analysis of CSF hypocretin-1 in type 1 and 2 narcolepsy |
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المؤلفون: | Ling Lin, Noriaki Sakai, Mari Matsumura, Emmanuel Mignot, Seiji Nishino |
المصدر: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-6 (2019) |
بيانات النشر: | Nature Publishing Group UK, 2019. |
سنة النشر: | 2019 |
مصطلحات موضوعية: | 0301 basic medicine, Adult, Male, medicine.medical_specialty, Radioimmunoassay, lcsh:Medicine, Peptide, HYPOCRETIN 1, Article, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Internal medicine, Medicine, Humans, lcsh:Science, Chromatography, High Pressure Liquid, Narcolepsy, chemistry.chemical_classification, Sleep disorder, Orexins, Multidisciplinary, business.industry, lcsh:R, Middle Aged, medicine.disease, Pathophysiology, 030104 developmental biology, Endocrinology, chemistry, Hypothalamus, lcsh:Q, Female, business, Peptides, 030217 neurology & neurosurgery, Biomarkers |
الوصف: | Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin (hcrt) neurons in the hypothalamus. Cerebrospinal fluid (CSF) hcrt-1 measurement has been well established as a gold standard of narcolepsy diagnosis, although some portions of narcoleptic patients show normal hcrt-1 levels. We aimed to examine peptide degradation of hcrt-1 and its abnormality in the CSF of patients by using high performance liquid chromatography (HPLC) followed by radioimmunoassay (RIA). CSF was collected from healthy controls, narcoleptic patients of type 1 with hcrt-1 deficiency, type 1 with normal hcrt-1 level, and type 2 with normal hcrt-1 level. We found that the majority of hcrt-1 immunoreactivity in extracted CSF was derived from unauthentic hcrt-1 peaks, which are predicted to be inactive metabolites, and the intact hcrt-1 peptide was less than 10% of the gross amount, suggesting that the regular RIA for CSF hcrt-1 measures largely reflect the unauthentic hcrt-1-related metabolites rather than the intact one. As expected, all hcrt-1-related peaks were abolished in type 1 with hcrt-1 deficiency. Importantly, we also found that the sum of the authentic hcrt-1 peptide (peaks 3 and 4) significantly decreased in non-deficient type 1 and tended to decrease in type 2 narcoleptic patients although the levels with the regular RIA in non-extracted CSF was equivalent to healthy controls. Immunoreactivity with unauthentic hcrt-1 metabolites may masks the possible decline in authentic hcrt-1 level caused by the partial loss of hcrt neurons. Our findings may provide new insights into the degradation of the hcrt-1 peptide and the pathophysiology of narcolepsy. |
اللغة: | English |
تدمد: | 2045-2322 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::97762c13c34151d823787e30dc91cbbeTest http://europepmc.org/articles/PMC6346108Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....97762c13c34151d823787e30dc91cbbe |
قاعدة البيانات: | OpenAIRE |
تدمد: | 20452322 |
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