Inflammatory bowel disease induces pathological α-synuclein aggregation in the human gut and brain
(2024) In Neuropathology and Applied Neurobiology 50(1).- Abstract
Aims: According to Braak's hypothesis, it is plausible that Parkinson's disease (PD) originates in the enteric nervous system (ENS) and spreads to the brain through the vagus nerve. In this work, we studied whether inflammatory bowel diseases (IBDs) in humans can progress with the emergence of pathogenic α-synuclein (α-syn) in the gastrointestinal tract and midbrain dopaminergic neurons. Methods: We have analysed the gut and the ventral midbrain from subjects previously diagnosed with IBD and form a DSS-based rat model of gut inflammation in terms of α-syn pathology. Results: Our data support the existence of pathogenic α-syn in both the gut and the brain, thus reinforcing the potential role of the ENS as a contributing factor in PD... (More)
Aims: According to Braak's hypothesis, it is plausible that Parkinson's disease (PD) originates in the enteric nervous system (ENS) and spreads to the brain through the vagus nerve. In this work, we studied whether inflammatory bowel diseases (IBDs) in humans can progress with the emergence of pathogenic α-synuclein (α-syn) in the gastrointestinal tract and midbrain dopaminergic neurons. Methods: We have analysed the gut and the ventral midbrain from subjects previously diagnosed with IBD and form a DSS-based rat model of gut inflammation in terms of α-syn pathology. Results: Our data support the existence of pathogenic α-syn in both the gut and the brain, thus reinforcing the potential role of the ENS as a contributing factor in PD aetiology. Additionally, we have analysed the effect of a DSS-based rat model of gut inflammation to demonstrate (i) the appearance of P-α-syn inclusions in both Auerbach's and Meissner's plexuses (gut), (ii) an increase in α-syn expression in the ventral mesencephalon (brain) and (iii) the degeneration of nigral dopaminergic neurons, which all are considered classical hallmarks in PD. Conclusion: These results strongly support the plausibility of Braak's hypothesis and emphasise the significance of peripheral inflammation and the gut-brain axis in initiating α-syn aggregation and transport to the substantia nigra, resulting in neurodegeneration.
(Less)
- author
- organization
-
- Neuroinflammation (research group)
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- LU Profile Area: Light and Materials
- LU Profile Area: Proactive Ageing
- LTH Profile Area: Nanoscience and Semiconductor Technology
- LINXS - Institute of advanced Neutron and X-ray Science
- NanoLund: Centre for Nanoscience
- Medical Microspectroscopy (research group)
- Department of Experimental Medical Science
- publishing date
- 2024-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- alpha-synuclein, inflammatory bowel disease, neurodegeneration, neuroinflammation, Parkinson's disease
- in
- Neuropathology and Applied Neurobiology
- volume
- 50
- issue
- 1
- article number
- e12962
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:38343067
- scopus:85184675081
- ISSN
- 0305-1846
- DOI
- 10.1111/nan.12962
- language
- English
- LU publication?
- yes
- id
- a977488c-ff06-4895-ba50-645b6d252815
- date added to LUP
- 2024-02-26 14:32:03
- date last changed
- 2024-08-02 08:11:12
@article{a977488c-ff06-4895-ba50-645b6d252815, abstract = {{<p>Aims: According to Braak's hypothesis, it is plausible that Parkinson's disease (PD) originates in the enteric nervous system (ENS) and spreads to the brain through the vagus nerve. In this work, we studied whether inflammatory bowel diseases (IBDs) in humans can progress with the emergence of pathogenic α-synuclein (α-syn) in the gastrointestinal tract and midbrain dopaminergic neurons. Methods: We have analysed the gut and the ventral midbrain from subjects previously diagnosed with IBD and form a DSS-based rat model of gut inflammation in terms of α-syn pathology. Results: Our data support the existence of pathogenic α-syn in both the gut and the brain, thus reinforcing the potential role of the ENS as a contributing factor in PD aetiology. Additionally, we have analysed the effect of a DSS-based rat model of gut inflammation to demonstrate (i) the appearance of P-α-syn inclusions in both Auerbach's and Meissner's plexuses (gut), (ii) an increase in α-syn expression in the ventral mesencephalon (brain) and (iii) the degeneration of nigral dopaminergic neurons, which all are considered classical hallmarks in PD. Conclusion: These results strongly support the plausibility of Braak's hypothesis and emphasise the significance of peripheral inflammation and the gut-brain axis in initiating α-syn aggregation and transport to the substantia nigra, resulting in neurodegeneration.</p>}}, author = {{Espinosa-Oliva, Ana M. and Ruiz, Rocío and Soto, Manuel Sarmiento and Boza-Serrano, Antonio and Rodriguez-Perez, Ana I. and Roca-Ceballos, María A. and García-Revilla, Juan and Santiago, Marti and Serres, Sébastien and Economopoulus, Vasiliki and Carvajal, Ana E. and Vázquez-Carretero, María D. and García-Miranda, Pablo and Klementieva, Oxana and Oliva-Martín, María J. and Deierborg, Tomas and Rivas, Eloy and Sibson, Nicola R. and Labandeira-García, José L. and Machado, Alberto and Peral, María J. and Herrera, Antonio J. and Venero, José L. and de Pablos, Rocío M.}}, issn = {{0305-1846}}, keywords = {{alpha-synuclein; inflammatory bowel disease; neurodegeneration; neuroinflammation; Parkinson's disease}}, language = {{eng}}, number = {{1}}, publisher = {{Wiley-Blackwell}}, series = {{Neuropathology and Applied Neurobiology}}, title = {{Inflammatory bowel disease induces pathological α-synuclein aggregation in the human gut and brain}}, url = {{http://dx.doi.org/10.1111/nan.12962}}, doi = {{10.1111/nan.12962}}, volume = {{50}}, year = {{2024}}, }