2007
DOI: 10.1073/pnas.0702717104
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Impaired dopamine release and synaptic plasticity in the striatum of PINK1 -deficient mice

Abstract: Parkinson's disease (PD) is characterized by the selective vulnerability of the nigrostriatal dopaminergic circuit. Recently, loss-offunction mutations in the PTEN-induced kinase 1 (PINK1) gene have been linked to early-onset PD. How PINK1 deficiency causes dopaminergic dysfunction and degeneration in PD patients is unknown. Here, we investigate the physiological role of PINK1 in the nigrostriatal dopaminergic circuit through the generation and multidisciplinary analysis of PINK1 ؊/؊ mutant mice. We found that… Show more

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Cited by 489 publications
(500 citation statements)
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“…The generation of the PINK1 gene-deficient mice was previously described (30). Age-matched syngenic male PINK1 +/+, +/−, −/− mice (10-12 wk, 22-26 g) were used in this study.…”
Section: Methodsmentioning
confidence: 99%
“…The generation of the PINK1 gene-deficient mice was previously described (30). Age-matched syngenic male PINK1 +/+, +/−, −/− mice (10-12 wk, 22-26 g) were used in this study.…”
Section: Methodsmentioning
confidence: 99%
“…Factors that regulate mitochondrial morphology have been shown to interact genetically with pink1 (5-7), and the pink1-deficient phenotype in Drosophila can be rescued by a component of the mitochondrial electron transport chain complex or a mitochondrial electron carrier (8,9). Respiratory chain defects have been reported in Pink1 Ϫ/Ϫ mouse embryonic fibroblasts (10), and some morphological and functional defects of mitochondria have been observed in the striatum of Pink1 null mice; Pink1 knock-out mice, however, do not exhibit any obvious morphological changes or loss of dopaminergic neurons in the substantia nigra (11,12). These findings indicate that PINK1 contributes to mitochondrial integrity.…”
mentioning
confidence: 99%
“…Because the measurements in this preparation reflect reuptake as well as release, the normalization of release by blocking reuptake in DJ-1-deficient mice suggests increased activity of the dopamine transporter, whereas the relative lack of effect in PINK1 knockouts suggests a primary defect in the release mechanism. Indeed, mice lacking PINK1 show less frequent as well as smaller individual release events from adrenal chromaffin cells (5). The authors further demonstrate defects in plasticity at the corticostriatal synapse that can be corrected with dopamine receptor agonists, dopamine supplementation, and amphetamine, supporting a specific, presynaptic defect in dopaminergic neurotransmission.…”
Section: Pink1mentioning
confidence: 83%
“…Similar to the DJ-1 knockout, PINK1-deficient mice show defects in evoked dopamine release measured by using striatal slices (5). However, these defects appear to differ, with inhibition of dopamine reuptake apparently normalizing the defect in release in the DJ-1 knockouts but not in the PINK1 (5,10,11). Because the measurements in this preparation reflect reuptake as well as release, the normalization of release by blocking reuptake in DJ-1-deficient mice suggests increased activity of the dopamine transporter, whereas the relative lack of effect in PINK1 knockouts suggests a primary defect in the release mechanism.…”
Section: Pink1mentioning
confidence: 90%
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