The purpose of this study was to evaluate the contribution of DT-diaphorase inhibition to in vivo neurodegenerative effects of dopamine (DA) oxidation to the corresponding o-quinones. The neurotoxicity to nigrostriatal DA neurons was induced by injection of manganese pyrophosphate (Mn(3+)) complex as a prooxidizing agent alone or together with the DT-diaphorase inhibitor dicumarol into the righ...

In order to gain insight into a possible modulatory role for mu, delta, and kappa opioid receptors of the nigrostriatal dopaminergic pathway, we investigated the topographical organization of the receptors with respect to pre- and postsynaptic membranes. Dopaminergic terminals projecting from the substantia nigra to the corpus striatum were destroyed by unilateral injection of 6-hydroxydopamine...

Parkinsonism, chorea, and dystonia are well-known clinical manifestations of Creutzfeldt-Jakob disease (CJD), but lesions of the nigrostriatal pathway have never been thoroughly studied. We performed a detailed neuropathologic study of the nigrostriatal pathway in 15 sporadic CJD and 2 variant CJD cases that included clinical correlations and assessment of neuron subtype loss, distribution of p...

Parkinson's disease (PD) manifests clinically as bradykinesia, rigidity, and development of a resting tremor, primarily due to degeneration of dopaminergic nigrostriatal pathways in the brain. Intranigral administration of the irreversible ubiquitin proteasome system inhibitor, lactacystin, has been used extensively to model nigrostriatal degeneration in rats, and study the effects of candidate...

This study examined whether ethyl pyruvate (EP) promotes the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. MPTP induced degeneration of nigrostriatal DA neurons and glial activation as visualized by tyrosine hydroxylase, macrophage Ag complex-1, and/or glial fibrillary acidic protein immunoreact...

The objective of the present study was to determine whether lesion of the subthalamic nucleus (STN) promoted by N-methyl-D-aspartate (NMDA) would rescue nigrostriatal dopaminergic neurons after unilateral 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). Initially, 16 mg 6-OHDA (6-OHDA group) or vehicle (artificial cerebrospinal fluid - aCSF; Sham group) was infused i...

This case report describes the induction of extrapyramidal symptoms with fluoxetine, which is reported to be a rare phenomenon. A dopamine blockade at the nigrostriatal level primarily mediated by serotonin has been proposed as the probable mechanism.

The vesicular monoamine transporter 2 (VMAT2; SLC18A2) is responsible for packaging dopamine into vesicles for subsequent release and has been suggested to serve a neuroprotective role in the dopamine system. Here, we show that mice that express approximately 5% of normal VMAT2 (VMAT2 LO) display age-associated nigrostriatal dopamine dysfunction that ultimately results in neurodegeneration. Ele...

Abnormal levels of brain iron have been reported in parkinsonism, which is characterized principally by degeneration of dopaminergic (DA) nigrostriatal neurons. There are conflicting reports, however, of both increased and decreased iron in parkinsonism. An animal model of parkinsonism was used to clarify the contribution of the loss of nigrostriatal DAergic neurons to abnormal iron accumulatio...

New therapeutic nonpharmacological methodology in Parkinson's disease (PD) involves cell and synaptic renewal or replacement to restore function of neuronal systems, including the dopaminergic (DA) system. Using fetal DA cell therapy in PD patients and laboratory models, it has been demonstrated that functional motor deficits associated with parkinsonism can be reduced. Similar results have bee...