Alpha-Synuclein Accumulation and Its Phosphorylation in the Enteric Nervous System of Patients Without Neurodegeneration: An Explorative Study
Alpha-synuclein (α-Syn) is widely distributed and involved in the regulation of the nervous system. The phosphorylation of α-Syn at serine 129 (pSer129α-Syn) is known to be closely associated with α-Synucleinopathies, especially Parkinson's disease (PD). The present study aimed to explore the α...
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Frontiers Media S.A.
2020-11-01
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Series: | Frontiers in Aging Neuroscience |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2020.575481/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lu-Lu Bu Lu-Lu Bu Kai-Xun Huang Kai-Xun Huang De-Zhi Zheng De-Zhi Zheng Dan-Yu Lin Dan-Yu Lin Ying Chen Ying Chen Xiu-Na Jing Xiu-Na Jing Yan-Ran Liang Yan-Ran Liang En-Xiang Tao En-Xiang Tao |
spellingShingle |
Lu-Lu Bu Lu-Lu Bu Kai-Xun Huang Kai-Xun Huang De-Zhi Zheng De-Zhi Zheng Dan-Yu Lin Dan-Yu Lin Ying Chen Ying Chen Xiu-Na Jing Xiu-Na Jing Yan-Ran Liang Yan-Ran Liang En-Xiang Tao En-Xiang Tao Alpha-Synuclein Accumulation and Its Phosphorylation in the Enteric Nervous System of Patients Without Neurodegeneration: An Explorative Study Frontiers in Aging Neuroscience α-Synuclein α-synucleinopathies enteric nervous system non-neurodegenerative disorder pathology |
author_facet |
Lu-Lu Bu Lu-Lu Bu Kai-Xun Huang Kai-Xun Huang De-Zhi Zheng De-Zhi Zheng Dan-Yu Lin Dan-Yu Lin Ying Chen Ying Chen Xiu-Na Jing Xiu-Na Jing Yan-Ran Liang Yan-Ran Liang En-Xiang Tao En-Xiang Tao |
author_sort |
Lu-Lu Bu |
title |
Alpha-Synuclein Accumulation and Its Phosphorylation in the Enteric Nervous System of Patients Without Neurodegeneration: An Explorative Study |
title_short |
Alpha-Synuclein Accumulation and Its Phosphorylation in the Enteric Nervous System of Patients Without Neurodegeneration: An Explorative Study |
title_full |
Alpha-Synuclein Accumulation and Its Phosphorylation in the Enteric Nervous System of Patients Without Neurodegeneration: An Explorative Study |
title_fullStr |
Alpha-Synuclein Accumulation and Its Phosphorylation in the Enteric Nervous System of Patients Without Neurodegeneration: An Explorative Study |
title_full_unstemmed |
Alpha-Synuclein Accumulation and Its Phosphorylation in the Enteric Nervous System of Patients Without Neurodegeneration: An Explorative Study |
title_sort |
alpha-synuclein accumulation and its phosphorylation in the enteric nervous system of patients without neurodegeneration: an explorative study |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Aging Neuroscience |
issn |
1663-4365 |
publishDate |
2020-11-01 |
description |
Alpha-synuclein (α-Syn) is widely distributed and involved in the regulation of the nervous system. The phosphorylation of α-Syn at serine 129 (pSer129α-Syn) is known to be closely associated with α-Synucleinopathies, especially Parkinson's disease (PD). The present study aimed to explore the α-Syn accumulation and its phosphorylation in the enteric nervous system (ENS) in patients without neurodegeneration. Patients who underwent colorectal surgery for either malignant or benign tumors that were not suitable for endoscopic resection (n = 19) were recruited to obtain normal intestinal specimens, which were used to assess α-Syn immunoreactivity patterns using α-Syn and pSer129α-Syn antibodies. Furthermore, the sub-location of α-Syn in neurons was identified by α-Syn/neurofilament double staining. Semi-quantitative counting was used to evaluate the expression of α-Syn and pSer129α-Syn in the ENS. Positive staining of α-Syn was detected in all intestinal layers in patients with non-neurodegenerative diseases. There was no significant correlation between the distribution of α-Syn and age (p = 0.554) or tumor stage (p = 0.751). Positive staining for pSer129α-Syn was only observed in the submucosa and myenteric plexus layers. The accumulation of pSer129α-Syn increased with age. In addition, we found that the degenerative changes of the ENS were related to the degree of tumor malignancy (p = 0.022). The deposits of α-Syn were present in the ENS of patients with non-neurodegenerative disorders; particularly the age-dependent expression of pSer129α-Syn in the submucosa and myenteric plexus. The current findings of α-Syn immunostaining in the ENS under near non-pathological conditions weaken the basis of using α-Syn pathology as a suitable hallmark to diagnose α-Synucleinopathies including PD. However, our data provided unique perspectives to study gastrointestinal dysfunction in non-neurodegenerative disorders. These findings provide new evidence to elucidate the neuropathological characteristics and α-Syn pathology pattern of the ENS in non-neurodegenerative conditions. |
topic |
α-Synuclein α-synucleinopathies enteric nervous system non-neurodegenerative disorder pathology |
url |
https://www.frontiersin.org/articles/10.3389/fnagi.2020.575481/full |
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doaj-8ae9dd5afcd74edcb369fa3dcd90fb082020-11-25T04:12:22ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652020-11-011210.3389/fnagi.2020.575481575481Alpha-Synuclein Accumulation and Its Phosphorylation in the Enteric Nervous System of Patients Without Neurodegeneration: An Explorative StudyLu-Lu Bu0Lu-Lu Bu1Kai-Xun Huang2Kai-Xun Huang3De-Zhi Zheng4De-Zhi Zheng5Dan-Yu Lin6Dan-Yu Lin7Ying Chen8Ying Chen9Xiu-Na Jing10Xiu-Na Jing11Yan-Ran Liang12Yan-Ran Liang13En-Xiang Tao14En-Xiang Tao15Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Neurology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDepartment of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Neurology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDepartment of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaAlpha-synuclein (α-Syn) is widely distributed and involved in the regulation of the nervous system. The phosphorylation of α-Syn at serine 129 (pSer129α-Syn) is known to be closely associated with α-Synucleinopathies, especially Parkinson's disease (PD). The present study aimed to explore the α-Syn accumulation and its phosphorylation in the enteric nervous system (ENS) in patients without neurodegeneration. Patients who underwent colorectal surgery for either malignant or benign tumors that were not suitable for endoscopic resection (n = 19) were recruited to obtain normal intestinal specimens, which were used to assess α-Syn immunoreactivity patterns using α-Syn and pSer129α-Syn antibodies. Furthermore, the sub-location of α-Syn in neurons was identified by α-Syn/neurofilament double staining. Semi-quantitative counting was used to evaluate the expression of α-Syn and pSer129α-Syn in the ENS. Positive staining of α-Syn was detected in all intestinal layers in patients with non-neurodegenerative diseases. There was no significant correlation between the distribution of α-Syn and age (p = 0.554) or tumor stage (p = 0.751). Positive staining for pSer129α-Syn was only observed in the submucosa and myenteric plexus layers. The accumulation of pSer129α-Syn increased with age. In addition, we found that the degenerative changes of the ENS were related to the degree of tumor malignancy (p = 0.022). The deposits of α-Syn were present in the ENS of patients with non-neurodegenerative disorders; particularly the age-dependent expression of pSer129α-Syn in the submucosa and myenteric plexus. The current findings of α-Syn immunostaining in the ENS under near non-pathological conditions weaken the basis of using α-Syn pathology as a suitable hallmark to diagnose α-Synucleinopathies including PD. However, our data provided unique perspectives to study gastrointestinal dysfunction in non-neurodegenerative disorders. These findings provide new evidence to elucidate the neuropathological characteristics and α-Syn pathology pattern of the ENS in non-neurodegenerative conditions.https://www.frontiersin.org/articles/10.3389/fnagi.2020.575481/fullα-Synucleinα-synucleinopathiesenteric nervous systemnon-neurodegenerative disorderpathology |