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The A9 dopaminergic (DA) neuronal group projecting to the dorsal striatum is the most vulnerable in Parkinson's disease (PD). We genetically engineered mouse embryonic stem (ES) cells to express the transcription factors Nurr1 or Pitx3. After in vitro differentiation of Pitx3-expressing ES cells, the proportion of DA neurons expressing aldehyde(More)
The neurotransmitter dopamine is integrally involved in the rewarding effects of drugs, and it has also been thought to mediate impulsive behaviors in animal models. Most of the studies of drug effects on impulsive behaviors in humans have involved drugs with complex actions on different transmitter systems and different receptor subtypes. The present study(More)
Biomarkers are urgently needed for the diagnosis and monitoring of disease progression in Parkinson's disease. Both DJ-1 and alpha-synuclein, two proteins critically involved in Parkinson's disease pathogenesis, have been tested as disease biomarkers in several recent studies with inconsistent results. These have been largely due to variation in the protein(More)
OBJECTIVE There is a clear need to develop biomarkers for Parkinson disease (PD) diagnosis, differential diagnosis of Parkinsonian disorders, and monitoring disease progression. We and others have demonstrated that a decrease in DJ-1 and/or α-synuclein in the cerebrospinal fluid (CSF) is a potential index for Parkinson disease diagnosis, but not for PD(More)
Despite successful treatment of Parkinson's disease (PD) with a wide variety of symptomatic therapy, the disease continues to progress and drug-resistance symptoms become the predominant factors producing the disability of PD patients. Neuroprotective therapies have been tested, but clinically effective drugs have not been found yet. New insights gained(More)
Treatment of Parkinson disease (PD) with L-3,4-dihydroxyphenylalanine (L-DOPA) dramatically relieves associated motor deficits, but L-DOPA-induced dyskinesias (LID) limit the therapeutic benefit over time. Previous investigations have noted changes in striatal medium spiny neurons, including abnormal activation of extracellular signal-regulated kinase1/2(More)
Neural precursors (NPs) derived from ventral mesencephalon (VM) normally generate dopaminergic (DA) neurons in vivo but lose their potential to differentiate into DA neurons during mitogenic expansion in vitro, hampering their efficient use as a transplantable and experimental cell source. Because embryonic stem (ES) cell-derived NPs (ES NP) do not go(More)
Nurr1 is a transcription factor critical for the development of midbrain dopaminergic (DA) neurons. This study modified mouse embryonic stem (ES) cells to constitutively express Nurr1 under the elongation factor-1alpha promoter. The Nurr1-expression in ES cells lead to up-regulation of all DA neuronal markers tested, resulting in about a 4- to 5-fold(More)
Deficits in forepaw adjusting steps in rats have been proposed as a non-drug-induced model of the akinesia associated with Parkinson's disease. The present study examined the relationship between contralateral forepaw adjusting steps and dopamine depletion after medial forebrain bundle lesions with 6-hydroxydopamine. Depletion of striatal dopamine by >80%(More)
Dopaminergic (DA) neurons in the ventral midbrain nuclei, substantia nigra pars compacta (SNc, A9) and ventral tegmental area (VTA, A10), play important roles in the control of movement, emotion, cognition, and reward related behavior. Although several transcription factors have been shown to be critical for midbrain DA neuron development, there has been no(More)