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Acute versus long-term effects of 6-hydroxydopamine on oxidative stress and dopamine depletion in the striatum of mice

Varcin, Mustafa and Bentea, Eduard and Mertens, Birgit and Van Den Haute, Chris and Baekelandt, Veerle and Michotte, Yvette and Sarre, Sophie (2011) Acute versus long-term effects of 6-hydroxydopamine on oxidative stress and dopamine depletion in the striatum of mice. Journal of Neuroscience Methods, 202 (2). pp. 128-136. ISSN 0165-0270

Type of Research: Article
Creators: Varcin, Mustafa and Bentea, Eduard and Mertens, Birgit and Van Den Haute, Chris and Baekelandt, Veerle and Michotte, Yvette and Sarre, Sophie
Description:

Oxidative stress is one of the mechanisms which may be important in the pathogenesis of Parkinson's disease. In the current study, the effects of 6-hydroxydopamine (6-OHDA) perfusion on hydroxyl radical formation in the mouse striatum were investigated using the in vivo salicylate trapping microdialysis technique. The latter uses salicylate as a trapping agent for hydroxyl radicals with formation of 2,3-dihydroxybenzoic acid (2,3-DHBA), which is measured by HPLC. Two different approaches of the technique were validated in mice. First, perfusion of the trapping agent salicylate (1 mM) via the probe in combination with 6-OHDA (5 μM) was used to screen for radical scavenging properties of compounds in mice. Alternatively, striatal administration of 6-OHDA in a concentration known to induce nigrostriatal denervation (1 mM), without the trapping agent, allowed to maximally challenge the neuronal microenvironment and as such to investigate both its acute and long-term effects. In the first method, as expected, glutathione (GSH) (1.5 mM) prevented the 6-OHDA-induced increase in 2,3-DHBA levels. In the second method, GSH prevented the hydroxyl radical formation, while depletion of GSH with 2-cyclohexen-1-one (CHO) resulted in significantly higher 2,3-DHBA levels than when 6-OHDA was perfused alone. Three weeks after the local 6-OHDA perfusion, the total striatal dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) content were reduced by 30%, compared to the intact striatum, accompanied by a reduction in striatal tyrosine hydroxylase (TH) immunoreactive (ir) nerve terminals. This suggests that the second method can be used to determine the acute as well as the long-term effects of 6-OHDA in the mouse striatum.

Official Website: http://dx.doi.org/10.1016/j.jneumeth.2011.07.004
Additional Information (Publicly available):

Published in Special Issue on the 13th International Conference on In Vivo Methods.

Keywords/subjects not otherwise listed: 6-Hydroxydopamine; Mice; Striatum; Oxidative stress; Microdialysis; Salicylate trapping
Publisher/Broadcaster/Company: Elsevier
Your affiliations with UAL: Colleges > London College of Fashion
Date: 15 November 2011
Digital Object Identifier: 10.1016/j.jneumeth.2011.07.004
Date Deposited: 01 Oct 2013 16:26
Last Modified: 01 Oct 2013 16:26
Item ID: 5988
URI: http://ualresearchonline.arts.ac.uk/id/eprint/5988

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