3,4-dihydroxyphenylalanine reverses the motor deficits in Pitx3-deficient aphakia mice: behavioral characterization of a novel genetic model of Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative disease characterized by a loss of dopaminergic neurons in the substantia nigra. There is a need for genetic animal models of PD for screening and in vivo testing of novel restorative therapeutic agents. Although current genetic models of PD produce behavioral impairment and nigrostriatal dysfunction, they do not reproduce the loss of midbrain dopaminergic neurons and 3,4-dihydroxyphenylalanine (L-DOPA) reversible behavioral deficits. Here, we demonstrate that Pitx3-deficient aphakia (ak) mice, which have been shown previously to exhibit a major loss of substantia nigra dopaminergic neurons, display motor deficits that are reversed by L-DOPA and evidence of "dopaminergic supersensitivity" in the striatum. Thus, ak mice represent a novel genetic model exhibiting useful characteristics to test the efficacy of symptomatic therapies for PD and to study the functional changes in the striatum after dopamine depletion and L-DOPA treatment.
Hwang
Dong-Youn
DY
Molecular Neurobiology Laboratory, McLean Hospital and Harvard Medical School, Belmont, Massachusetts 02478, USA.
Fleming
Sheila M
SM
Ardayfio
Paul
P
Moran-Gates
Taylor
T
Kim
Hansoo
H
Tarazi
Frank I
FI
Chesselet
Marie-Francoise
MF
Kim
Kwang-Soo
KS
D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001259:Ataxia / Q000188:drug therapy / Q000235:genetics; D001545:Benserazide / Q000627:therapeutic use; D001766:Blindness / Q000235:genetics; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D007980:Levodopa / Q000627:therapeutic use*; D008124:Locomotion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000235:genetics; D011597:Psychomotor Performance / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics
D000978:Antiparkinson Agents; D018398:Homeodomain Proteins; D014157:Transcription Factors; C433629:homeobox protein PITX3; D007980:Levodopa; D001545:Benserazide; D004298:Dopamine
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