Brain-Derived Major Glycoproteins Are Possible Biomarkers for Altered Metabolism of Cerebrospinal Fluid in Neurological Diseases
Cerebrospinal fluid (CSF) plays an important role in the homeostasis of the brain. We previously reported that CSF major glycoproteins are biosynthesized in the brain, i.e., lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin isoforms carrying unique glycans. Although these glycoprotei...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6084 |
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| author | Kyoka Hoshi Mayumi Kanno Aya Goto Yoshikazu Ugawa Katsutoshi Furukawa Hiroyuki Arai Masakazu Miyajima Koichi Takahashi Kotaro Hattori Keiichi Kan Takashi Saito Yoshiki Yamaguchi Takashi Mitsufuji Nobuo Araki Yasuhiro Hashimoto |
| author_facet | Kyoka Hoshi Mayumi Kanno Aya Goto Yoshikazu Ugawa Katsutoshi Furukawa Hiroyuki Arai Masakazu Miyajima Koichi Takahashi Kotaro Hattori Keiichi Kan Takashi Saito Yoshiki Yamaguchi Takashi Mitsufuji Nobuo Araki Yasuhiro Hashimoto |
| author_sort | Kyoka Hoshi |
| collection | DOAJ |
| description | Cerebrospinal fluid (CSF) plays an important role in the homeostasis of the brain. We previously reported that CSF major glycoproteins are biosynthesized in the brain, i.e., lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin isoforms carrying unique glycans. Although these glycoproteins are secreted from distinct cell types, their CSF levels have been found to be highly correlated with each other in cases of neurodegenerative disorders. The aim of this study was to examine these marker levels and their correlations in other neurological diseases, such as depression and schizophrenia, and disorders featuring abnormal CSF metabolism, including spontaneous intracranial hypotension (SIH) and idiopathic normal pressure hydrocephalus (iNPH). Brain-derived marker levels were found to be highly correlated with each other in the CSF of depression and schizophrenia patients. SIH is caused by CSF leakage, which is suspected to induce hypovolemia and a compensatory increase in CSF production. In SIH, the brain-derived markers were 2–3-fold higher than in other diseases, and, regardless of their diverse levels, they were found to be correlated with each other. Another abnormality of the CSF metabolism, iNPH, is possibly caused by the reduced absorption of CSF, which secondarily induces CSF accumulation in the ventricle; the excess CSF compresses the brain’s parenchyma to induce dementia. One potential treatment is a “shunt operation” to bypass excess CSF from the ventricles to the peritoneal cavity, leading to the attenuation of dementia. After the shunt operation, marker levels began to increase within a week and then further increased by 2–2.5-fold at three, six, and twelve months post-operation, at which point symptoms had gradually attenuated. Notably, the marker levels were found to be correlated with each other in the post-operative period. In conclusion, the brain-derived major glycoprotein markers were highly correlated in the CSF of patients with different neurological diseases, and their correlations were maintained even after surgical intervention. These results suggest that brain-derived proteins could be biomarkers of CSF production. |
| first_indexed | 2024-03-11T05:35:56Z |
| format | Article |
| id | doaj.art-88c102a750004e4cb10702d7e9fe1c92 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:35:56Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-88c102a750004e4cb10702d7e9fe1c922023-11-17T16:46:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247608410.3390/ijms24076084Brain-Derived Major Glycoproteins Are Possible Biomarkers for Altered Metabolism of Cerebrospinal Fluid in Neurological DiseasesKyoka Hoshi0Mayumi Kanno1Aya Goto2Yoshikazu Ugawa3Katsutoshi Furukawa4Hiroyuki Arai5Masakazu Miyajima6Koichi Takahashi7Kotaro Hattori8Keiichi Kan9Takashi Saito10Yoshiki Yamaguchi11Takashi Mitsufuji12Nobuo Araki13Yasuhiro Hashimoto14Department of Biochemistry, Fukushima Medical University, Fukushima City 960-1295, Fukushima, JapanDepartment of Forensic Medicine, Fukushima Medical University, Fukushima City 960-1295, Fukushima, JapanCenter for Integrated Science and Humanities, Fukushima Medical University, Fukushima City 960-1295, Fukushima, JapanDepartment of Human Neurophysiology, Fukushima Medical University, Fukushima City 960-1295, Fukushima, JapanDivision of Community Medicine, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Miyagi, JapanInstitute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Miyagi, JapanDepartment of Neurosurgery, Juntendo University, Bunkyo City 113-8421, Tokyo, JapanDepartment of Neurosurgery, Sanno Hospital, Minato City 107-0052, Tokyo, JapanDepartment of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira 187-8502, Tokyo, JapanDepartment of Anesthesiology, Southern Tohoku General Hospital, Koriyama 963-8052, Fukushima, JapanDepartment of Neurocognitive Science, Nagoya City University, Nagoya 467-8601, Aichi, JapanLaboratory of Pharmaceutical Physical Chemistry, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Miyagi, JapanDepartment of Neurology, Saitama Medical University Hospital, Koshigaya 350-0495, Saitama, JapanDepartment of Neurology, Saitama Medical University Hospital, Koshigaya 350-0495, Saitama, JapanDepartment of Forensic Medicine, Fukushima Medical University, Fukushima City 960-1295, Fukushima, JapanCerebrospinal fluid (CSF) plays an important role in the homeostasis of the brain. We previously reported that CSF major glycoproteins are biosynthesized in the brain, i.e., lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin isoforms carrying unique glycans. Although these glycoproteins are secreted from distinct cell types, their CSF levels have been found to be highly correlated with each other in cases of neurodegenerative disorders. The aim of this study was to examine these marker levels and their correlations in other neurological diseases, such as depression and schizophrenia, and disorders featuring abnormal CSF metabolism, including spontaneous intracranial hypotension (SIH) and idiopathic normal pressure hydrocephalus (iNPH). Brain-derived marker levels were found to be highly correlated with each other in the CSF of depression and schizophrenia patients. SIH is caused by CSF leakage, which is suspected to induce hypovolemia and a compensatory increase in CSF production. In SIH, the brain-derived markers were 2–3-fold higher than in other diseases, and, regardless of their diverse levels, they were found to be correlated with each other. Another abnormality of the CSF metabolism, iNPH, is possibly caused by the reduced absorption of CSF, which secondarily induces CSF accumulation in the ventricle; the excess CSF compresses the brain’s parenchyma to induce dementia. One potential treatment is a “shunt operation” to bypass excess CSF from the ventricles to the peritoneal cavity, leading to the attenuation of dementia. After the shunt operation, marker levels began to increase within a week and then further increased by 2–2.5-fold at three, six, and twelve months post-operation, at which point symptoms had gradually attenuated. Notably, the marker levels were found to be correlated with each other in the post-operative period. In conclusion, the brain-derived major glycoprotein markers were highly correlated in the CSF of patients with different neurological diseases, and their correlations were maintained even after surgical intervention. These results suggest that brain-derived proteins could be biomarkers of CSF production.https://www.mdpi.com/1422-0067/24/7/6084cerebrospinal fluidchoroid plexusneuronprostaglandin D2 synthasebrain-derived transferrinneurological diseases |
| spellingShingle | Kyoka Hoshi Mayumi Kanno Aya Goto Yoshikazu Ugawa Katsutoshi Furukawa Hiroyuki Arai Masakazu Miyajima Koichi Takahashi Kotaro Hattori Keiichi Kan Takashi Saito Yoshiki Yamaguchi Takashi Mitsufuji Nobuo Araki Yasuhiro Hashimoto Brain-Derived Major Glycoproteins Are Possible Biomarkers for Altered Metabolism of Cerebrospinal Fluid in Neurological Diseases International Journal of Molecular Sciences cerebrospinal fluid choroid plexus neuron prostaglandin D2 synthase brain-derived transferrin neurological diseases |
| title | Brain-Derived Major Glycoproteins Are Possible Biomarkers for Altered Metabolism of Cerebrospinal Fluid in Neurological Diseases |
| title_full | Brain-Derived Major Glycoproteins Are Possible Biomarkers for Altered Metabolism of Cerebrospinal Fluid in Neurological Diseases |
| title_fullStr | Brain-Derived Major Glycoproteins Are Possible Biomarkers for Altered Metabolism of Cerebrospinal Fluid in Neurological Diseases |
| title_full_unstemmed | Brain-Derived Major Glycoproteins Are Possible Biomarkers for Altered Metabolism of Cerebrospinal Fluid in Neurological Diseases |
| title_short | Brain-Derived Major Glycoproteins Are Possible Biomarkers for Altered Metabolism of Cerebrospinal Fluid in Neurological Diseases |
| title_sort | brain derived major glycoproteins are possible biomarkers for altered metabolism of cerebrospinal fluid in neurological diseases |
| topic | cerebrospinal fluid choroid plexus neuron prostaglandin D2 synthase brain-derived transferrin neurological diseases |
| url | https://www.mdpi.com/1422-0067/24/7/6084 |
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