Chronic corticosterone enhancement aggravates alpha-synuclein brain spreading pathology and substantia nigra neurodegeneration in mice

Burtscher, J.; Copin, J.-C.; Rodrigues, J.; Thangaraj, S. K.; Chiki, A.; Guillot de Suduiraut, M.-I.; Sandi, C.; Lashuel, H. A.

doi:10.1101/469999

bioRxiv · 10.1101/469999

Chronic corticosterone enhancement aggravates alpha-synuclein brain spreading pathology and substantia nigra neurodegeneration in mice

Burtscher, J.·Copin, J.-C.·Rodrigues, J.·Thangaraj, S. K.·Chiki, A.·Guillot de Suduiraut, M.-I.·Sandi, C.·Lashuel, H. A.

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Abstract

Chronic stress and associated heightened glucocorticoid levels are risk factors for depression, a common non-motor symptom in Parkinsons disease (PD). However, how heightened glucocorticoids influence PD neuropathology [alpha-synuclein (-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 -Syn pathology, neurodegeneration, behavior and mitochondrial function in a mouse model of -Syn pathology spreading after intracerebral injection of -Syn preformed fibrils (PFFs). Our results demonstrate that heightened corticosterone aggravates neurodegeneration and -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.

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Burtscher, J., Copin, J.-C., Rodrigues, J., Thangaraj, S. K., Chiki, A., Guillot de Suduiraut, M.-I., Sandi, C., Lashuel, H. A.. 2018-11-17. Chronic corticosterone enhancement aggravates alpha-synuclein brain spreading pathology and substantia nigra neurodegeneration in mice. https://doi.org/10.1101/469999

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