Chronic corticosterone aggravates behavioral and neuronal symptomatology in a mouse model of alpha-synuclein pathology

NEUROBIOLOGY OF AGING

卷:83

Article

Burtscher, Johannes¹  Copin, Jean-Christophe¹  Rodrigues, Joao²  Kumar, Senthil T.¹  Chiki, Anass¹  de Suduiraut, Isabelle Guillot²  Sandi, Carmen²  Lashuel, Hilal A.¹ 

[1] Ecole Polytech Fed Lausanne, Brain Mind Inst, Lab Mol & Chem Biol Neurodegenerat, Al 2-151,Stn 19, CH-1015 Lausanne, Switzerland

[2] Ecole Polytech Fed Lausanne, Brain Mind Inst, Lab Behav Genet, Lausanne, Switzerland

关键词: Synuclein;    Parkinson's disease;    Neurodegeneration;    Chronic stress;    Depression;    Conditioning;   

DOI  :  10.1016/j.neurobiolaging.2019.08.007

来源: Elsevier

【 摘 要 】

Debilitating, yet underinvestigated nonmotor symptoms related to mood/emotion, such as depression, are common in Parkinson's disease. Here, we explore the role of depression and of the amygdala, a brain region robustly linked to mood/emotion, in synucleinopathy. We hypothesized that mood/emotional deficits might accelerate Parkinson's disease-linked symptomatology, including the formation of alpha-synuclein pathology. We combined elevated corticosterone treatment, modeling chronic stress and depression, with a model of seeded alpha-synuclein pathology in mouse striatum and assessed behavioral parameters with a focus on mood/emotion, and neuropathology. We report behavioral resilience against alpha-synuclein proteinopathy in the absence of additional insults, potentially based on hormesis/conditioning mechanisms. Elevated corticosterone, however, reversed alpha-synuclein pathology-induced behavioral adaptations and was associated with increased dopaminergic cell loss as well as aggravated alpha-synuclein pathology in specific brain regions, such as the entorhinal cortex. These findings point to elevated glucocorticoids as a risk factor for Parkinson's disease progression and highlight the potential of glucocorticoid level reducing strategies to slow down disease progression in synucleinopathy. (C) 2019 The Authors. Published by Elsevier Inc.

【 授权许可】

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