Characterisation of behavioural and neurodegenerative changes induced by intranigral 6-hydroxydopamine lesions in a mouse model of Parkinson's disease.
Despite the widespread use of mice as models of Parkinson's disease there is a surprising lack of validation and characterisation of unilateral lesion models in mice and the extent of behavioural impairments induced by such lesions. The aim of the present study was to characterise the behavioural deficits observed after injection of 6-hydroxydopamine unilaterally into the substantia nigra, and correlate the behavioural impairments with the extent of damage to the mesostriatal dopaminergic pathway. We found that a recently introduced test for assessment of sensorimotor impairment, the corridor task, was particularly useful in determining lesion severity, and that this test, in combination with standard drug-induced rotation tests, can be used to select animals with profound (> or = 80%) dopaminergic lesions that are stable over time. Based on these data we propose criteria that can be used to predict the extent of lesion, classified as severe, intermediate or mild lesions of the mesostriatal pathway. The correlation of cell loss and striatal innervation with the performance in each test provides a useful tool for the assessment of functional recovery in neurorestoration and cell transplantation studies, and for the evaluation of the in vivo efficacy and performance of stem cell-derived dopamine neuron preparations.
Wallenberg Neuroscience Center, Department of Experimental Medical Sciences, Lund University, BMC A11, Lund 22184, Sweden. shane.grealish@med.lu.se
Shane
S
Grealish
Bengt
B
Mattsson
Peter
P
Draxler
Anders
A
Björklund
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D051379:Mice; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology; D009483:Neuropsychological Tests; D016627:Oxidopamine / Q000494:pharmacology*; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013565:Sympatholytics / Q000494:pharmacology*
D015259:Dopamine Agents; D018491:Dopamine Agonists; D013565:Sympatholytics; D016627:Oxidopamine; D000661:Amphetamine; D001058:Apomorphine; D004298:Dopamine