• the Korean Society for Brain and Neural Sciences


Original Article

Exp Neurobiol 2011; 20(4): 181-188

Published online December 30, 2011

© The Korean Society for Brain and Neural Sciences

Transmission of Synucleinopathies in the Enteric Nervous System of A53T Alpha-Synuclein Transgenic Mice

He-Jin Lee2, Ji-Eun Suk1, Kyung-Won Lee1, Seung-Hwa Park2, Peter C. Blumbergs3, Wei-Ping Gai4 and Seung-Jae Lee1*

1Department of Biomedical Science and Technology, SMART IABS, and 2Department of Anatomy, School of Medicine, Konkuk University, Seoul 143-701, Korea, 3Hanson Institute Centre for Neurological Diseases, Institute of Medical and Veterinary Science, SA Pathology, Adelaide, South Australia, 4Department of Human Physiology and Centre for Neuroscience, Flinders University School of Medicine, Bedford Park SA 5042, Australia

Correspondence to: *To whom correspondence should be addressed.
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Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are characterized by abnormal deposition of α-synuclein aggregates in many regions of the central and peripheral nervous systems. Accumulating evidence suggests that the α-synuclein pathology initiates in a few discrete regions and spreads to larger areas in the nervous system. Recent pathological studies of PD patients have raised the possibility that the enteric nervous system is one of the initial sites of α-synuclein aggregation and propagation. Here, we evaluated the induction and propagation of α-synuclein aggregates in the enteric nervous system of the A53T α-synuclein transgenic mice after injection of human brain tissue extracts into the gastric walls of the mice. Western analysis of the brain extracts showed that the DLB extract contained detergent-stable α-synuclein aggregates, but the normal brain extract did not. Injection of the DLB extract resulted in an increased deposition of α-synuclein in the myenteric neurons, in which α-synuclein formed punctate aggregates over time up to 4 months. In these mice, inflammatory responses were increased transiently at early time points. None of these changes were observed in the A53T mice injected with saline or the normal brain extract, nor were these found in the wild type mice injected with the DLB extract. These results demonstrate that pathological α-synuclein aggregates present in the brain of DLB patient can induce the aggregation of endogenous α-synuclein in the myenteric neurons in A53T mice, suggesting the transmission of synucleinopathy lesions in the enteric nervous system.

Keywords: enteric nervous system, Parkinson's disease, dementia with Lewy bodies, protein aggregation, Lewy body, inflammation