Behavioral characterization of a unilateral 6-OHDA-lesion model of Parkinson's disease in mice.
Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Several toxin-induced animals models simulate the motor deficits occurring in PD. Among them, the unilateral 6-hydroxydopamine (6-OHDA) model is frequently used in rats and has the advantage of presenting side-biased motor impairments. However, the behavioral consequences of a unilateral 6-OHDA-lesion have, so far, not been described in detail in mice. The aim of this study was to characterize mice with unilateral 6-OHDA-lesions placed in the median forebrain bundle using several motor behavioral tests in order to identify the most suitable predictor of nigral cell loss. Mice underwent various drug-induced (amphetamine- and apomorphine-induced rotation) and spontaneous motor tests (cylinder, rotarod, elevated body swing, and stride length test). The amphetamine-induced rotation test, the cylinder and the rotarod test were most sensitive and reliable in detecting loss of tyrosine hydroxylase-immunoreactive cells in the substantia nigra. This study demonstrates that substantial and stable unilateral 6-OHDA-induced lesions can be established in mice, and that these lesions can be functionally assessed using several different side-bias-based behavioral tests. This mouse model offers the opportunity to use transgenic mouse strains and study the interactions between genes of interest and toxins in relation to Parkinson's disease etiology in the future.
Iancu
Ruxandra
R
Neuronal Survival Unit, Wallenberg Neuroscience Centre, Department of Experimental Medical Sciences, Lunds University, BMC A10, 22184 Lund, Sweden.
Mohapel
Paul
P
Brundin
Patrik
P
Paul
Gesine
G
D018663:Adrenergic Agents; D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D016014:Linear Models; D008474:Medial Forebrain Bundle / Q000293:injuries / Q000503:physiopathology; D051379:Mice; D008808:Mice, Inbred CBA; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine; D010300:Parkinson Disease / Q000209:etiology / Q000503:physiopathology*; D011237:Predictive Value of Tests; D011597:Psychomotor Performance / Q000187:drug effects; D045442:Rotarod Performance Test / Q000379:methods; D012399:Rotation; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism
D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine