TY - JOUR
T1 - Characterization of the striatal 6-OHDA model of Parkinson's disease in wild type and α-synuclein-deleted mice
AU - Alvarez-Fischer, Daniel
AU - Henze, Carmen
AU - Strenzke, Corinna
AU - Westrich, Jan
AU - Ferger, Boris
AU - Höglinger, Günter U.
AU - Oertel, Wolfgang H.
AU - Hartmann, Andreas
PY - 2008/3/1
Y1 - 2008/3/1
N2 - Genetically modified mice models are increasingly used to study the pathophysiology of Parkinson's disease (PD), particularly in conditions where they are subjected to toxins specific for dopaminergic neurons. The most widely used toxin in these paradigms is 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), although it presents a number of drawbacks regarding (i) the kinetics of neurodegeneration, (ii) strain-specificity and (iii) partial lesion recovery. 6-hydroxydopamine (6-OHDA) may be an alternative tool since it leads to a partial damage of DA terminals and to a delayed and progressive loss of nigral DA neurons. It is frequently used in rats and well characterized in this species. In mice, however, this model has not been described in detail to date. The aim of the present study was to characterize the time course of intra-striatal 6-OHDA lesions in mice with regard to i) dopaminergic cell loss, ii) dopamine concentrations in the substantia nigra and the striatum, iii) hydroxylation products in substantia nigra and striatum and iv) behavioural impairment. Furthermore, we used α-synuclein-deleted mice, which have been studied extensively in MPTP paradigms, and examined their reactivity to intra-striatal 6-OHDA injections. Intra-striatally injected 6-OHDA leads to a long-lasting dopamine depletion of the nigro-striatal pathway, whereas behavioural parameters partially recovered over a two month period. Its toxicity seems to be influenced by α-synuclein, since α-synuclein-deleted mice are more resistant against 6-OHDA than their wild type littermates. In summary, we propose that the striatal 6-OHDA model may be a valuable addition and/or alternative in genetically modified mice models used in the study of PD pathophysiology.
AB - Genetically modified mice models are increasingly used to study the pathophysiology of Parkinson's disease (PD), particularly in conditions where they are subjected to toxins specific for dopaminergic neurons. The most widely used toxin in these paradigms is 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), although it presents a number of drawbacks regarding (i) the kinetics of neurodegeneration, (ii) strain-specificity and (iii) partial lesion recovery. 6-hydroxydopamine (6-OHDA) may be an alternative tool since it leads to a partial damage of DA terminals and to a delayed and progressive loss of nigral DA neurons. It is frequently used in rats and well characterized in this species. In mice, however, this model has not been described in detail to date. The aim of the present study was to characterize the time course of intra-striatal 6-OHDA lesions in mice with regard to i) dopaminergic cell loss, ii) dopamine concentrations in the substantia nigra and the striatum, iii) hydroxylation products in substantia nigra and striatum and iv) behavioural impairment. Furthermore, we used α-synuclein-deleted mice, which have been studied extensively in MPTP paradigms, and examined their reactivity to intra-striatal 6-OHDA injections. Intra-striatally injected 6-OHDA leads to a long-lasting dopamine depletion of the nigro-striatal pathway, whereas behavioural parameters partially recovered over a two month period. Its toxicity seems to be influenced by α-synuclein, since α-synuclein-deleted mice are more resistant against 6-OHDA than their wild type littermates. In summary, we propose that the striatal 6-OHDA model may be a valuable addition and/or alternative in genetically modified mice models used in the study of PD pathophysiology.
UR - http://www.scopus.com/inward/record.url?scp=39449113020&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2007.10.012
DO - 10.1016/j.expneurol.2007.10.012
M3 - Journal articles
C2 - 18053987
AN - SCOPUS:39449113020
SN - 0014-4886
VL - 210
SP - 182
EP - 193
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -