Unit:
Κατεύθυνση ΝευροεπιστήμεςLibrary of the School of Science
Author:
Antoniou Christine
Supervisors info:
Leonidas Stefanis Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research
Foundation of the Academy of Athens (BRFAA), 4 Soranou Efesiou St, 11527 Athens, Greece; 1st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece. Electronic address: lstefanis@bioacademy.gr
Maria Xilouri Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research
Foundation of the Academy of Athens (BRFAA), 4 Soranou Efesiou St, 11527 Athens, Greece. Electronic address: mxilouri@bioacademy.gr.
Panagiotis Politis Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, 4 Soranou Efesiou Street, 115 27 Athens, Greece Electronic address: ppolitis@bioacademy.gr
Original Title:
CHRONIC STRESS DRIVES ALPHA-SYNUCLEIN ASSOCIATED PATHOLOGY : AN IN VIVO STUDY
Translated title:
CHRONIC STRESS DRIVES ALPHA-SYNUCLEIN ASSOCIATED PATHOLOGY : AN IN VIVO STUDY
Summary:
Parkinson’s disease (PD) is the fastest growing neurodegenerative disorder with a
prevalence of approximately 1-2% in the worldwide population over 60 years of age.
Alpha-synuclein (aSyn) is a presynaptic neuronal protein strongly associated with PD
pathology in genetic and idiopathic forms of the disease. Moreover, there is growing
amount of evidence implicating chronic stress and its sequelae - neuroinflammation
and neurodegeneration - in PD pathogenesis. Nevertheless, the interplay between
aSyn and chronic stress, and its potential contribution to neurodegeneration and PD
pathology remains elusive. In this study, we used a transgenic rat model
overexpressing the wildtype human alpha-synuclein gene, SNCA, (aSyn BAC rats) to
investigate the effects of chronic stress (psychological and pharmacological) on PD-
associated pathologies. We provide evidence that chronic corticosterone
administration enhances phosphorylated aSyn (pS129) burden in the hypothalamus -
the initiator of the stress response - and that it fuels neurodegeneration across the
nigrostriatal axis. We also demonstrated that psychological stress (i.e. chronic
unpredictable stress) is implicated in striatal neuroinflammation and alters the
hippocampal transcriptome of different pathways associated with autophagy,
synaptic function, inflammation and oxidative stress. Our results contribute to a
better understanding of the complex interaction between aSyn and brain stress
system function, and highlight chronic stress as a potential driver of PD.
Main subject category:
Science
Other subject categories:
Health Sciences
Keywords:
Parkinson’s disease, HPA axis, alpha-synuclein, corticosterone, chronic stress
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Research thesis_Antoniou Christine.pdf
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