Author:
Burtscher Johannes,Copin Jean-Christophe,Rodrigues João,Thangaraj Senthil K.,Chiki Anass,de Suduiraut Marie-Isabelle Guillot,Sandi Carmen,Lashuel Hilal A.
Abstract
AbstractChronic stress and associated heightened glucocorticoid levels are risk factors for depression, a common non-motor symptom in Parkinson’s disease (PD). However, how heightened glucocorticoids influence PD neuropathology [alpha-synuclein (α-Syn) containing Lewy pathology and neurodegeneration] and disease progression is unclear. To address this knowledge gap, we investigated the impact of chronic corticosterone administration on α-Syn pathology, neurodegeneration, behavior and mitochondrial function in a mouse model of α-Syn pathology spreading after intracerebral injection of α-Syn preformed fibrils (PFFs). Our results demonstrate that heightened corticosterone aggravates neurodegeneration and α-Syn pathology spreading, intriguingly to specific brain regions, such as the entorhinal cortex. Corticosterone-treatment abolished distinct physiological adaptations after PFF-injection and induced differential physiological and behavioral consequences. Taken together, our work points to elevated glucocorticoids as a risk factor for the development of the neuropathological hallmarks of PD. Strategies aimed at reducing glucocorticoid levels might slow down pathology spreading and disease progression in synucleinopathy.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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