Unknown

Dataset Information

0

The organic cation transporter-3 is a pivotal modulator of neurodegeneration in the nigrostriatal dopaminergic pathway.


ABSTRACT: Toxic organic cations can damage nigrostriatal dopaminergic pathways as seen in most parkinsonian syndromes and in some cases of illicit drug exposure. Here, we show that the organic cation transporter 3 (Oct3) is expressed in nondopaminergic cells adjacent to both the soma and terminals of midbrain dopaminergic neurons. We hypothesized that Oct3 contributes to the dopaminergic damage by bidirectionally regulating the local bioavailability of toxic species. Consistent with this view, Oct3 deletion and pharmacological inhibition hampers the release of the toxic organic cation 1-methyl-4-phenylpyridinium from astrocytes and protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration in mice. Furthermore, Oct3 deletion impairs the removal of the excess extracellular dopamine induced by methamphetamine and enhances striatal dopaminergic terminal damage caused by this psychostimulant. These results may have far-reaching implications for our understanding of the mechanism of cell death in a wide range of neurodegenerative diseases and may open new avenues for neuroprotective intervention.

SUBMITTER: Cui M 

PROVIDER: S-EPMC2683105 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

The organic cation transporter-3 is a pivotal modulator of neurodegeneration in the nigrostriatal dopaminergic pathway.

Cui Mei M   Aras Radha R   Christian Whitney V WV   Rappold Phillip M PM   Hatwar Mamata M   Panza Joseph J   Jackson-Lewis Vernice V   Javitch Jonathan A JA   Ballatori Nazzareno N   Przedborski Serge S   Tieu Kim K  

Proceedings of the National Academy of Sciences of the United States of America 20090429 19


Toxic organic cations can damage nigrostriatal dopaminergic pathways as seen in most parkinsonian syndromes and in some cases of illicit drug exposure. Here, we show that the organic cation transporter 3 (Oct3) is expressed in nondopaminergic cells adjacent to both the soma and terminals of midbrain dopaminergic neurons. We hypothesized that Oct3 contributes to the dopaminergic damage by bidirectionally regulating the local bioavailability of toxic species. Consistent with this view, Oct3 deleti  ...[more]

Similar Datasets

| S-EPMC3080980 | biostudies-literature
| S-EPMC2824790 | biostudies-literature
| S-EPMC9640557 | biostudies-literature
| S-EPMC9687798 | biostudies-literature
| S-EPMC1851987 | biostudies-literature
| S-EPMC3775896 | biostudies-literature
| S-EPMC7178762 | biostudies-literature
| S-EPMC4757596 | biostudies-literature
| S-EPMC8195675 | biostudies-literature
| S-EPMC8657912 | biostudies-literature