title: Similar L-dopa-stimulated motor activity in mice with adult-onset 6-hydroxydopamine-induced symmetric dopamine denervation and in transcription factor Pitx3 null mice with perinatal-onset symmetric dopamine denervation.
abstract: The transcription factor Pitx3 null mutant (Pitx3Null) mice have a constitutive perinatal-onset and symmetric bilateral dopamine (DA) loss in the striatum. In these mice l-3,4-dihydroxyphenylalanine (l-dopa) induces apparently normal horizontal movements (walking) but also upward movements consisting of the vertical body trunk and waving paws that are absent in normal animals and in animals with the classic unilateral 6-hydroxydopamine (6-OHDA) lesion-induced DA denervation. Thus, a concern is that the perinatal timing of the DA loss and potential developmental abnormalities in Pitx3Null mice may underlie these upward movements, thus reducing the usefulness as a DA denervation model. Here we show that in normal wild-type (Pitx3WT) mice with adult-onset symmetric, bilateral 6-OHDA-induced DA lesion in the dorsal striatum, l-dopa induces normal horizontal movements and upward movements that are qualitatively identical to those in Pitx3Null mice. Furthermore, after unilateral 6-OHDA lesion of the residual DA innervation in the striatum in Pitx3Null mice, l-dopa induces contraversive rotation that is similar to that in Pitx3WT mice with the classic unilateral 6-OHDA lesion. These results indicate that in Pitx3Null mice, the bilateral symmetric DA denervation in the dorsal striatum is sufficient for expressing the l-dopa-induced motor phenotype and the perinatal timing of their DA loss is not a determining factor, providing further evidence that Pitx3Null mice are a convenient and suitable mouse model to study the consequences of DA loss and dopaminergic replacement therapy in Parkinson's disease.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA; School of Biotechnology, Southern Medical University, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Sagot
authors.affiliation: Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: fzhou3@uthsc.edu.
authors.forename: Fu-Ming
authors.initials: FM
authors.lastname: Zhou
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology*; D018398:Homeodomain Proteins / Q000235:genetics; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; C433629:homeobox protein PITX3; D007980:Levodopa; D016627:Oxidopamine
keywords: 6-hydroxydopamine (6-OHDA); Basal ganglia; Dopamine receptor supersensitivity; Motor asymmetry; Parkinson׳s disease; l-3,4-dihydroxyphenylalanine (l-dopa)