3,4-Dihydroxyphenylalanine Reverses the Motor Deficits in Pitx3-Deficient<i>Aphakia</i>Mice: Behavioral Characterization of a Novel Genetic Model of Parkinson's Disease

書誌事項

公開日
2005-02-23
権利情報
  • https://creativecommons.org/licenses/by-nc-sa/4.0/
DOI
  • 10.1523/jneurosci.3718-04.2005
公開者
Society for Neuroscience

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説明

<jats:p>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<jats:italic>in vivo</jats:italic>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 (<jats:sc>l</jats:sc>-DOPA) reversible behavioral deficits. Here, we demonstrate that Pitx3-deficient<jats:italic>aphakia</jats:italic>(<jats:italic>ak</jats:italic>) mice, which have been shown previously to exhibit a major loss of substantia nigra dopaminergic neurons, display motor deficits that are reversed by<jats:sc>l</jats:sc>-DOPA and evidence of “dopaminergic supersensitivity” in the striatum. Thus,<jats:italic>ak</jats:italic>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<jats:sc>l</jats:sc>-DOPA treatment.</jats:p>

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