Unit:
Κατεύθυνση ΝευροεπιστήμεςLibrary of the School of Science
Supervisors info:
Λεωνίδας Στεφανής, MD, PhD, Καθηγητής Νευρολογίας και Νευροβιολογίας Ιατρικής Σχολής Παν/μίου Αθηνών και Συνεργαζόμενος Ερευνητής στο Ίδρυμα Ιατροβιολογικών Ερευνών της Ακαδημίας Αθηνών.
Αλεξία Πολυσίδη, PhD, Διδάκτωρ Φαρμακολογίας, Επιστημονική Συνεργάτης, Ίδρυμα Ιατροβιολογικών Ερευνών της Ακαδημίας Αθηνών.
Original Title:
Modulators of alpha-synuclein-mediated neurodegeneration: Evaluation of an in vitro stress modality on alpha-synuclein transcriptional regulation, expression, accumulation, and aggregation in cultured primary hippocampal neurons derived from wild-type and humanized alpha-synuclein rats.
Translated title:
Modulators of alpha-synuclein-mediated neurodegeneration: Evaluation of an in vitro stress modality on alpha-synuclein transcriptional regulation, expression, accumulation, and aggregation in cultured primary hippocampal neurons derived from wild-type and humanized alpha-synuclein rats.
Summary:
Chronic stress has been proposed as one of the environmental triggers of Parkinson’s disease. Alpha-synuclein overexpression is linked genetically to Parkinson’s disease but also pathologically as toxic forms of the protein and aggregates are present in post mortem patient brains. Here, we show that the synthetic glucocorticoid, dexamethasone, has effects on transcription, expression and secretion of a-synuclein in wildtype and BAC human alpha-synuclein overexpressing-transgenic primary hippocampal and cortical neuronal cultures. Dexamethasone treatment up-regulates rat and human SNCA mRNA both in hippocampal and cortical primary neuronal cultures. This dexamethasone-driven up regulation translates into a-synuclein overexpression and higher levels of phosphorylated (pSER-129) alpha-synuclein primarily in primary hippocampal neuronal cultures. There is an absence of dexamethasone-dose dependent secretion of a-synuclein both in primary hippocampal and cortical cultured condition media. In BAC-transgenic cultured condition media secreted a-synuclein protein levels are higher, even in baseline conditions, compared to WT cultured condition media both in hippocampus and cortex.
Main subject category:
Science
Keywords:
stress, alpha-synuclein, Parkinson's disease, transcriptional regulation, primary hippocampal neuronal cultures
