Recent clinical evidence supports a link between 25-hydroxyvitamin D insufficiency (serum 25-hydroxyvitamin D [25(OH)D] levels <30 ng/mL) and Parkinson's disease. To investigate the effect of 25(OH)D depletion on neuronal susceptibility to toxic insult, we induced a state of 25(OH)D deficiency in mice and then challenged them with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydro...

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 bidire...

Single photon emission computed tomography (SPECT) and the dopamine (DA) transporter tracer, 2 beta-carboxymethoxy-3 beta-(4-iodophenyl)tropane ([123I]beta-CIT), were used to determine DA transporter density in 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-lesioned monkeys with varying degrees of parkinsonism. The clinical stage of parkinsonism corresponded to SPECT measures of striatal ...

Nigrostriatal damage is increased in males relative to females. While estrogen is neuroprotective in females, less is known about potential protective effects of testosterone in males. We determined if castration enhances neuronal injury to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Castrates or sham-castrated mice were sacrificed 1 week following injection of MPTP (4 × 20 mg/kg) or s...

Recent evidence indicates that cyclin-dependent kinases (CDKs, cdks) may be inappropriately activated in several neurodegenerative conditions. Here, we report that cdk5 expression and activity are elevated after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin that damages the nigrostriatal dopaminergic pathway. Supporting the pathogenic significance of the cdk5 al...

Striatal dopamine (DA) denervation results in a significant loss of dendritic spines on medium spiny projection neurons in Parkinson's disease. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated parkinsonian monkeys, spines contacted either by cortical or thalamic glutamatergic terminals are severely affected on both direct and indirect striatofugal neurons. In rodents, indirect pathway ne...

Animal models of Parkinson's disease with dementia would greatly facilitate research into the underlying causes of this disorder. Here, we showed that bilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the substantia nigra pars compacta (SNc) of Wistar rats caused degeneration of nigrostriatal dopaminergic neurons, cell loss in the hippocampal CA1 area, as well as mi...

Objective To investigate the protective effects of nicotine on dopaminergic neurons. Methods C57BL/6J mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (20mg/kg) to establish Parkinson’s disease (PD) model after pretreated with nicotine(0.25 mg/kg). The effects of nicotine to PD mice were observed by their behavior test and immunocytochemistry staining (ICC) for tyrosi...

The role of microtubule (MT) dysfunction in Parkinson's disease is emerging. It is still unknown whether it is a cause or a consequence of neurodegeneration. Our objective was to assess whether alterations of MT stability precede or follow axonal transport impairment and neurite degeneration in experimental parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57Bl mic...

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes parkinsonism in humans and nonhuman animals, and its use has led to greater understanding of the pathogenesis of Parkinson's disease. However, its molecular targets have not been defined. We show that mice lacking the gene for poly(ADP-ribose) polymerase (PARP), which catalyzes the attachment of ADP ribose units fro...