Title: Acute versus long-term effects of 6-hydroxydopamine on oxidative stress and dopamine depletion in the striatum of mice
Authors: Varcin, Mustafa
Bentea, Eduard
Mertens, Birgit
Van Den Haute, Chris
Baekelandt, Veerle
Michotte, Yvette
Sarre, Sophie # ×
Issue Date: Nov-2011
Publisher: Elsevier/North-Holland
Series Title: Journal of Neuroscience Methods vol:202 issue:2 pages:128-136
Abstract: 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 (1mM) via the probe in combination with 6-OHDA (5μM) 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 (1mM), 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) (1.5mM) 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.
ISSN: 0165-0270
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group for Neurobiology and Gene Therapy
× corresponding author
# (joint) last author

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