Increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosis
Abstract Background Extracellular adenosine 5'-triphosphate (ATP) has been suggested to cause neuroinflammation and motor neuron degeneration by activating microglia and astrocytes in amyotrophic lateral sclerosis (ALS). Since we have developed a highly sensitive ATP assay system, we examined c...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2021-06-01
|
Series: | BMC Neurology |
Subjects: | |
Online Access: | https://doi.org/10.1186/s12883-021-02288-4 |
id |
doaj-692b371a4acd49159c2c061308de8b87 |
---|---|
record_format |
Article |
spelling |
doaj-692b371a4acd49159c2c061308de8b872021-07-04T11:15:28ZengBMCBMC Neurology1471-23772021-06-012111810.1186/s12883-021-02288-4Increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosisTakamasa Nukui0Atsushi Matsui1Hideki Niimi2Tomoyuki Sugimoto3Tomohiro Hayashi4Nobuhiro Dougu5Hirofumi Konishi6Mamoru Yamamoto7Ryoko Anada8Noriyuki Matsuda9Isao Kitajima10Yuji Nakatsuji11Department of Neurology, Faculty of Medicine, University of ToyamaDepartment of Clinical Laboratory and Molecular Pathology, Graduate School of Medicine and Pharmaceutical Science for Research, University of ToyamaDepartment of Clinical Laboratory and Molecular Pathology, Graduate School of Medicine and Pharmaceutical Science for Research, University of ToyamaFaculty of Data Science, Graduate School of Data Science, University of ShigaDepartment of Neurology, Faculty of Medicine, University of ToyamaDepartment of Neurology, Faculty of Medicine, University of ToyamaDepartment of Neurology, Faculty of Medicine, University of ToyamaDepartment of Neurology, Faculty of Medicine, University of ToyamaDepartment of Neurology, Faculty of Medicine, University of ToyamaDepartment of Neurology, Faculty of Medicine, University of ToyamaDepartment of Clinical Laboratory and Molecular Pathology, Graduate School of Medicine and Pharmaceutical Science for Research, University of ToyamaDepartment of Neurology, Faculty of Medicine, University of ToyamaAbstract Background Extracellular adenosine 5'-triphosphate (ATP) has been suggested to cause neuroinflammation and motor neuron degeneration by activating microglia and astrocytes in amyotrophic lateral sclerosis (ALS). Since we have developed a highly sensitive ATP assay system, we examined cerebrospinal fluid (CSF) ATP levels in patients with ALS whether it can be a useful biomarker in ALS. Methods Forty-eight CSF samples from 44 patients with ALS were assayed for ATP with a newly established, highly sensitive assay system using luciferase luminous reaction. CSF samples from patients with idiopathic normal pressure hydrocephalus (iNPH) were assayed as a control. Patients were divided into two groups depending on their disease severity, as evaluated using the Medical Research Council (MRC) sum score. Correlations between the CSF ATP levels and other factors, including clinical data and serum creatinine levels, were evaluated. Results CSF ATP levels were significantly higher in patients with ALS than in the iNPH (716 ± 411 vs. 3635 ± 5465 pmol/L, p < 0.01). CSF ATP levels were significantly higher in the more severe group than in the iNPH group (6860 ± 8312 vs. 716 ± 411 pmol/L, p < 0.05) and mild group (6860 ± 8312 vs. 2676 ± 3959 pmol/L, p < 0.05) respectively. ALS functional rating scale-revised (ALSFRS-R) (37.9 ± 5.7 vs. 42.4 ± 2.8, p < 0.01) and serum creatinine levels (0.51 ± 0.13 vs. 0.68 ± 0.23 mg/dL, p < 0.05) were significantly lower in the severe group than in the mild group respectively. A negative correlation of CSF ATP levels with MRC sum score was demonstrated in the correlation analysis adjusted for age and sex (r = -0.3, p = 0.08). Conclusions Extracellular ATP is particularly increased in the CSF of patients with advanced ALS. CSF ATP levels may be a useful biomarker for evaluating disease severity in patients with ALS.https://doi.org/10.1186/s12883-021-02288-4ALSCerebrospinal fluidATPBiomarker |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Takamasa Nukui Atsushi Matsui Hideki Niimi Tomoyuki Sugimoto Tomohiro Hayashi Nobuhiro Dougu Hirofumi Konishi Mamoru Yamamoto Ryoko Anada Noriyuki Matsuda Isao Kitajima Yuji Nakatsuji |
spellingShingle |
Takamasa Nukui Atsushi Matsui Hideki Niimi Tomoyuki Sugimoto Tomohiro Hayashi Nobuhiro Dougu Hirofumi Konishi Mamoru Yamamoto Ryoko Anada Noriyuki Matsuda Isao Kitajima Yuji Nakatsuji Increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosis BMC Neurology ALS Cerebrospinal fluid ATP Biomarker |
author_facet |
Takamasa Nukui Atsushi Matsui Hideki Niimi Tomoyuki Sugimoto Tomohiro Hayashi Nobuhiro Dougu Hirofumi Konishi Mamoru Yamamoto Ryoko Anada Noriyuki Matsuda Isao Kitajima Yuji Nakatsuji |
author_sort |
Takamasa Nukui |
title |
Increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosis |
title_short |
Increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosis |
title_full |
Increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosis |
title_fullStr |
Increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosis |
title_full_unstemmed |
Increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosis |
title_sort |
increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosis |
publisher |
BMC |
series |
BMC Neurology |
issn |
1471-2377 |
publishDate |
2021-06-01 |
description |
Abstract Background Extracellular adenosine 5'-triphosphate (ATP) has been suggested to cause neuroinflammation and motor neuron degeneration by activating microglia and astrocytes in amyotrophic lateral sclerosis (ALS). Since we have developed a highly sensitive ATP assay system, we examined cerebrospinal fluid (CSF) ATP levels in patients with ALS whether it can be a useful biomarker in ALS. Methods Forty-eight CSF samples from 44 patients with ALS were assayed for ATP with a newly established, highly sensitive assay system using luciferase luminous reaction. CSF samples from patients with idiopathic normal pressure hydrocephalus (iNPH) were assayed as a control. Patients were divided into two groups depending on their disease severity, as evaluated using the Medical Research Council (MRC) sum score. Correlations between the CSF ATP levels and other factors, including clinical data and serum creatinine levels, were evaluated. Results CSF ATP levels were significantly higher in patients with ALS than in the iNPH (716 ± 411 vs. 3635 ± 5465 pmol/L, p < 0.01). CSF ATP levels were significantly higher in the more severe group than in the iNPH group (6860 ± 8312 vs. 716 ± 411 pmol/L, p < 0.05) and mild group (6860 ± 8312 vs. 2676 ± 3959 pmol/L, p < 0.05) respectively. ALS functional rating scale-revised (ALSFRS-R) (37.9 ± 5.7 vs. 42.4 ± 2.8, p < 0.01) and serum creatinine levels (0.51 ± 0.13 vs. 0.68 ± 0.23 mg/dL, p < 0.05) were significantly lower in the severe group than in the mild group respectively. A negative correlation of CSF ATP levels with MRC sum score was demonstrated in the correlation analysis adjusted for age and sex (r = -0.3, p = 0.08). Conclusions Extracellular ATP is particularly increased in the CSF of patients with advanced ALS. CSF ATP levels may be a useful biomarker for evaluating disease severity in patients with ALS. |
topic |
ALS Cerebrospinal fluid ATP Biomarker |
url |
https://doi.org/10.1186/s12883-021-02288-4 |
work_keys_str_mv |
AT takamasanukui increasedcerebrospinalfluidadenosine5triphosphateinpatientswithamyotrophiclateralsclerosis AT atsushimatsui increasedcerebrospinalfluidadenosine5triphosphateinpatientswithamyotrophiclateralsclerosis AT hidekiniimi increasedcerebrospinalfluidadenosine5triphosphateinpatientswithamyotrophiclateralsclerosis AT tomoyukisugimoto increasedcerebrospinalfluidadenosine5triphosphateinpatientswithamyotrophiclateralsclerosis AT tomohirohayashi increasedcerebrospinalfluidadenosine5triphosphateinpatientswithamyotrophiclateralsclerosis AT nobuhirodougu increasedcerebrospinalfluidadenosine5triphosphateinpatientswithamyotrophiclateralsclerosis AT hirofumikonishi increasedcerebrospinalfluidadenosine5triphosphateinpatientswithamyotrophiclateralsclerosis AT mamoruyamamoto increasedcerebrospinalfluidadenosine5triphosphateinpatientswithamyotrophiclateralsclerosis AT ryokoanada increasedcerebrospinalfluidadenosine5triphosphateinpatientswithamyotrophiclateralsclerosis AT noriyukimatsuda increasedcerebrospinalfluidadenosine5triphosphateinpatientswithamyotrophiclateralsclerosis AT isaokitajima increasedcerebrospinalfluidadenosine5triphosphateinpatientswithamyotrophiclateralsclerosis AT yujinakatsuji increasedcerebrospinalfluidadenosine5triphosphateinpatientswithamyotrophiclateralsclerosis |
_version_ |
1721320524541329408 |