Neurobiology of disease · 2022
Thoracic trauma promotes alpha-Synuclein oligomerization in murine Parkinson's disease.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Ruf Wolfgang P, Palmer Annette, Dörfer Lena, Wiesner Diana, Buck Eva, Grozdanov Veselin, Kassubek Jan, Dimou Leda, Ludolph Albert C, Huber-Lang Markus, Danzer Karin M
Аннотация
BACKGROUND: Systemic and neuroinflammatory processes play key roles in neurodegenerative diseases such as Parkinson's disease (PD). Physical trauma which induces considerable systemic inflammatory responses, represents an evident environmental factor in aging. However, little is known about the impact of physical trauma, on the immuno-pathophysiology of PD. Especially blunt chest trauma which is associated with a high morbidity and mortality rate in the elderly population, can induce a strong pulmonary and systemic inflammatory reaction. Hence, we sought out to combine a well-established thoracic trauma mouse model with a well-established PD mouse model to characterize the influence of physical trauma to neurodegenerative processes in PD.
METHODS: To study the influence of peripheral trauma in a PD mouse model we performed a highly standardized blunt thorax trauma in a well-established PD mouse model and determined the subsequent local and systemic response.
RESULTS: We could show that blunt chest trauma leads to a systemic inflammatory response which is quantifiable with increased inflammatory markers in bronchoalveolar fluids (BALF) and plasma regardless of the presence of a PD phenotype. A difference of the local inflammatory response in the brain between the PD group and non-PD group could be detected, as well as an increase in the formation of oligomeric pathological alpha-Synuclein (asyn) suggesting an interplay between peripheral thoracic trauma and asyn pathology in PD.
CONCLUSION: Taken together this study provides evidence that physical trauma is associated with increased asyn oligomerization in a PD mouse model underlining the relevance of PD pathogenesis under traumatic settings.
METHODS: To study the influence of peripheral trauma in a PD mouse model we performed a highly standardized blunt thorax trauma in a well-established PD mouse model and determined the subsequent local and systemic response.
RESULTS: We could show that blunt chest trauma leads to a systemic inflammatory response which is quantifiable with increased inflammatory markers in bronchoalveolar fluids (BALF) and plasma regardless of the presence of a PD phenotype. A difference of the local inflammatory response in the brain between the PD group and non-PD group could be detected, as well as an increase in the formation of oligomeric pathological alpha-Synuclein (asyn) suggesting an interplay between peripheral thoracic trauma and asyn pathology in PD.
CONCLUSION: Taken together this study provides evidence that physical trauma is associated with increased asyn oligomerization in a PD mouse model underlining the relevance of PD pathogenesis under traumatic settings.