Dose-dependent loss of motor function after unilateral medial forebrain bundle rotenone lesion in rats: A cautionary note
Identifieur interne : 001954 ( Main/Exploration ); précédent : 001953; suivant : 001955Dose-dependent loss of motor function after unilateral medial forebrain bundle rotenone lesion in rats: A cautionary note
Auteurs : Alexander Klein [Canada] ; Darryl C. Gidyk [Canada] ; Alexandra M. Shriner [Canada] ; Keri L. Colwell [Canada] ; Nadine A. Tatton [Canada] ; William G. Tatton [Canada] ; Gerlinde A. Metz [Canada]Source :
- Behavioural brain research [ 0166-4328 ] ; 2011.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
The organic pesticide rotenone is a neurotoxin suspected to cause Parkinson's disease (PD) symptoms by selectively targeting and compromising the survival of dopaminergic neurons. Rotenone in rodent models reproduces key features of human PD by impairing the mitochondrial electron transport chain, leading to intracellular alpha-synuclein aggregates and functional impairments typical for PD. The present study characterized the dose-response relationship of standard rotenone concentrations in motor impairments in a rat model. Rats received a single medial forebrain bundle injection of 4, 8, or 12 μg of rotenone. Animals were assessed in skilled limb use, skilled and non-skilled walking and exploratory activity as well as drug-induced rotation. The results revealed rotational bias and stable impairments in skilled walking and gross motor function up to five weeks post injection. However, transient motor deficits facilitated rapid improvement of skilled reaching success. Mainly the temporal aspects of skilled and non-skilled motor performance were responsive to different rotenone concentrations. By contrast, drug-induced rotation and nigral TH+ cell loss were not influenced by different rotenone doses. Rats infused with 8 μg and 12 μg seemed to have reached a ceiling effect in motor deficits as they were not distinguishable in behavioral measures. Most strikingly, the stereological and morphological analyses revealed non-specific toxicity of vehicle and rotenone infusions that caused macroscopic lesions beyond nigral boundaries. These findings suggest that sensitivity of comprehensive motor tests to subtle modulation of dopamine function is independent of dopamine cell loss per se. Furthermore, caution is advised concerning non-specific toxicity of rotenone and vehicle substances in experimental animal models.
Affiliations:
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Tatton</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge</s1><s2>Lethbridge, Alberta T1K 3M4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Lethbridge, Alberta T1K 3M4</wicri:noRegion></affiliation></author><author><name sortKey="Metz, Gerlinde A" sort="Metz, Gerlinde A" uniqKey="Metz G" first="Gerlinde A." last="Metz">Gerlinde A. Metz</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge</s1><s2>Lethbridge, Alberta T1K 3M4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Lethbridge, Alberta T1K 3M4</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Behavioural brain research</title><title level="j" type="abbreviated">Behav. brain res.</title><idno type="ISSN">0166-4328</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Behavioural brain research</title><title level="j" type="abbreviated">Behav. brain res.</title><idno type="ISSN">0166-4328</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal</term><term>Body movement</term><term>Dopamine</term><term>Lesion</term><term>Medial forebrain bundle</term><term>Motor skill</term><term>Motricity</term><term>Parkinson disease</term><term>Rat</term><term>Rotenone</term><term>Toxin</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Motricité</term><term>Faisceau médian télencéphale</term><term>Lésion</term><term>Maladie de Parkinson</term><term>Dopamine</term><term>Toxine</term><term>Habileté motrice</term><term>Mouvement corporel</term><term>Rat</term><term>Animal</term><term>Roténone</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The organic pesticide rotenone is a neurotoxin suspected to cause Parkinson's disease (PD) symptoms by selectively targeting and compromising the survival of dopaminergic neurons. Rotenone in rodent models reproduces key features of human PD by impairing the mitochondrial electron transport chain, leading to intracellular alpha-synuclein aggregates and functional impairments typical for PD. The present study characterized the dose-response relationship of standard rotenone concentrations in motor impairments in a rat model. Rats received a single medial forebrain bundle injection of 4, 8, or 12 μg of rotenone. Animals were assessed in skilled limb use, skilled and non-skilled walking and exploratory activity as well as drug-induced rotation. The results revealed rotational bias and stable impairments in skilled walking and gross motor function up to five weeks post injection. However, transient motor deficits facilitated rapid improvement of skilled reaching success. Mainly the temporal aspects of skilled and non-skilled motor performance were responsive to different rotenone concentrations. By contrast, drug-induced rotation and nigral TH+ cell loss were not influenced by different rotenone doses. Rats infused with 8 μg and 12 μg seemed to have reached a ceiling effect in motor deficits as they were not distinguishable in behavioral measures. Most strikingly, the stereological and morphological analyses revealed non-specific toxicity of vehicle and rotenone infusions that caused macroscopic lesions beyond nigral boundaries. These findings suggest that sensitivity of comprehensive motor tests to subtle modulation of dopamine function is independent of dopamine cell loss per se. Furthermore, caution is advised concerning non-specific toxicity of rotenone and vehicle substances in experimental animal models.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Klein, Alexander" sort="Klein, Alexander" uniqKey="Klein A" first="Alexander" last="Klein">Alexander Klein</name></noRegion><name sortKey="Colwell, Keri L" sort="Colwell, Keri L" uniqKey="Colwell K" first="Keri L." last="Colwell">Keri L. Colwell</name><name sortKey="Gidyk, Darryl C" sort="Gidyk, Darryl C" uniqKey="Gidyk D" first="Darryl C." last="Gidyk">Darryl C. Gidyk</name><name sortKey="Metz, Gerlinde A" sort="Metz, Gerlinde A" uniqKey="Metz G" first="Gerlinde A." last="Metz">Gerlinde A. Metz</name><name sortKey="Shriner, Alexandra M" sort="Shriner, Alexandra M" uniqKey="Shriner A" first="Alexandra M." last="Shriner">Alexandra M. Shriner</name><name sortKey="Tatton, Nadine A" sort="Tatton, Nadine A" uniqKey="Tatton N" first="Nadine A." last="Tatton">Nadine A. Tatton</name><name sortKey="Tatton, William G" sort="Tatton, William G" uniqKey="Tatton W" first="William G." last="Tatton">William G. Tatton</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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