Do alpha-synuclein vector injections provide a better model of Parkinson's disease than the classic 6-hydroxydopamine model?

Lindgren, Hanna S., Lelos, Mariah Jillian ORCID: https://orcid.org/0000-0001-7102-055X and Dunnett, Stephen Bruce ORCID: https://orcid.org/0000-0003-1826-1578 2012. Do alpha-synuclein vector injections provide a better model of Parkinson's disease than the classic 6-hydroxydopamine model? Experimental Neurology 237 (1) , pp. 36-42. 10.1016/j.expneurol.2012.05.022

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Abstract

Improvements in modelling Parkinson's disease in rodents contribute to the advancement of scientific knowledge and open innumerable pathways for the development of new therapeutic interventions. In a recent article in this journal, Decressac and co-workers present an interesting comparison between two classic 6-hydroxydopamine (6-OHDA) models and the more recently established rodent model of Parkinson's disease induced by over-expression of α-synuclein using adeno-associated viral vectors. As expected, injections of 6-OHDA result in extensive loss of dopamine associated with pronounced motor deficits. Interestingly, over-expression of α-synuclein in the substantia nigra pars compacta also results in a considerable loss of dopamine as well as motor impairments. Both the level of dopamine loss and the motor deficits seen after α-synuclein over-expression were similar in extent to that seen after intrastriatal injections of 6-OHDA, but the temporal profile of degeneration and the development of motor deficits were progressive, more closely mimicking the clinical condition. This commentary offers further insights into the differences between these two rodent models, and asks how well they each replicate idiopathic PD. In addition, the translational relevance, reliability, and predictive value of this more recently developed AAV α-synuclein model are considered.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	Elsevier
ISSN:	0014-4886
Last Modified:	09 Jun 2023 06:40
URI:	https://orca.cardiff.ac.uk/id/eprint/41693

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