Author Of 1 Presentation
PS10.02 - The Enteric Nervous System as a Potential Autoimmune Target in Multiple Sclerosis
Abstract
Abstract
Background
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) and the most frequent neurological disorder in young adults that leads to irreversible deficits and premature retirement. The etiology of MS is still unclear, although genetic predisposition, viral infections, vitamin D deficiency and dietary components along with microbiome dysbalance are discussed as potential risk factors.
Objectives
The presentation as outlined here will provide novel insights into current paradigm shifts regarding our understanding of the disease. In particular, it will be discussed whether MS pathology is restricted to the CNS or whether also peripheral organs have to be considered as disease starting points, in particular the gut. Over 60% of patients complain of gastrointestinal dysfunction and over 30% of patients report such symptoms even before the onset of MS.
Methods
Experimental autoimmune encephalomyelitis (EAE), which is the common mouse model of MS, was used to study enteric nervous system (ENS) pathology by histology, immunohistochemistry and electron microscopy of paraffin and ultra-thin sections as well as whole mounts of both the submucosal and myenteric plexus. Functional analyses comprised measurements of the gastrointestinal transit time and local gut wall motility. Results were transferred to the human disease by performing assessment of colon resectates from MS patients.
Results
Our results show that pathology of the ENS occured prior to CNS degeneration, in particular in the myenteric plexus. This pathology was antibody-mediated and involved autoantigenic targets that are shared between ENS and CNS such as myelin basic protein (MBP) and proteolipid protein (PLP). Pathology was accompanied by significantly reduced gut motility. Likewise, analysis of colon resectates from MS patients revealed nerve fiber degeneration and enterogliosis of the myenteric plexus.
Conclusions
Further research is needed to corroborate these findings in a larger patient cohort and to unravel the etiology of ENS degeneration. Interestingly, ENS involvement is increasingly discussed also in Parkinson’s and Alzheimer’s disease as well as in amyotrophic lateral sclerosis so that there might be a common denominator for several neurodegenerative disorders.
Presenter Of 1 Presentation
PS10.02 - The Enteric Nervous System as a Potential Autoimmune Target in Multiple Sclerosis
Abstract
Abstract
Background
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) and the most frequent neurological disorder in young adults that leads to irreversible deficits and premature retirement. The etiology of MS is still unclear, although genetic predisposition, viral infections, vitamin D deficiency and dietary components along with microbiome dysbalance are discussed as potential risk factors.
Objectives
The presentation as outlined here will provide novel insights into current paradigm shifts regarding our understanding of the disease. In particular, it will be discussed whether MS pathology is restricted to the CNS or whether also peripheral organs have to be considered as disease starting points, in particular the gut. Over 60% of patients complain of gastrointestinal dysfunction and over 30% of patients report such symptoms even before the onset of MS.
Methods
Experimental autoimmune encephalomyelitis (EAE), which is the common mouse model of MS, was used to study enteric nervous system (ENS) pathology by histology, immunohistochemistry and electron microscopy of paraffin and ultra-thin sections as well as whole mounts of both the submucosal and myenteric plexus. Functional analyses comprised measurements of the gastrointestinal transit time and local gut wall motility. Results were transferred to the human disease by performing assessment of colon resectates from MS patients.
Results
Our results show that pathology of the ENS occured prior to CNS degeneration, in particular in the myenteric plexus. This pathology was antibody-mediated and involved autoantigenic targets that are shared between ENS and CNS such as myelin basic protein (MBP) and proteolipid protein (PLP). Pathology was accompanied by significantly reduced gut motility. Likewise, analysis of colon resectates from MS patients revealed nerve fiber degeneration and enterogliosis of the myenteric plexus.
Conclusions
Further research is needed to corroborate these findings in a larger patient cohort and to unravel the etiology of ENS degeneration. Interestingly, ENS involvement is increasingly discussed also in Parkinson’s and Alzheimer’s disease as well as in amyotrophic lateral sclerosis so that there might be a common denominator for several neurodegenerative disorders.
Invited Speaker Of 1 Presentation
PS10.02 - The Enteric Nervous System as a Potential Autoimmune Target in Multiple Sclerosis
Abstract
Abstract
Background
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) and the most frequent neurological disorder in young adults that leads to irreversible deficits and premature retirement. The etiology of MS is still unclear, although genetic predisposition, viral infections, vitamin D deficiency and dietary components along with microbiome dysbalance are discussed as potential risk factors.
Objectives
The presentation as outlined here will provide novel insights into current paradigm shifts regarding our understanding of the disease. In particular, it will be discussed whether MS pathology is restricted to the CNS or whether also peripheral organs have to be considered as disease starting points, in particular the gut. Over 60% of patients complain of gastrointestinal dysfunction and over 30% of patients report such symptoms even before the onset of MS.
Methods
Experimental autoimmune encephalomyelitis (EAE), which is the common mouse model of MS, was used to study enteric nervous system (ENS) pathology by histology, immunohistochemistry and electron microscopy of paraffin and ultra-thin sections as well as whole mounts of both the submucosal and myenteric plexus. Functional analyses comprised measurements of the gastrointestinal transit time and local gut wall motility. Results were transferred to the human disease by performing assessment of colon resectates from MS patients.
Results
Our results show that pathology of the ENS occured prior to CNS degeneration, in particular in the myenteric plexus. This pathology was antibody-mediated and involved autoantigenic targets that are shared between ENS and CNS such as myelin basic protein (MBP) and proteolipid protein (PLP). Pathology was accompanied by significantly reduced gut motility. Likewise, analysis of colon resectates from MS patients revealed nerve fiber degeneration and enterogliosis of the myenteric plexus.
Conclusions
Further research is needed to corroborate these findings in a larger patient cohort and to unravel the etiology of ENS degeneration. Interestingly, ENS involvement is increasingly discussed also in Parkinson’s and Alzheimer’s disease as well as in amyotrophic lateral sclerosis so that there might be a common denominator for several neurodegenerative disorders.