scholarly journals Cue-induced striatal dopamine release in Parkinson's disease-associated impulsive-compulsive behaviours

Brain ◽  
2011 ◽  
Vol 134 (4) ◽  
pp. 969-978 ◽  
Author(s):  
S. S. O'Sullivan ◽  
K. Wu ◽  
M. Politis ◽  
A. D. Lawrence ◽  
A. H. Evans ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine Release ◽  
Striatal Dopamine ◽  
Striatal Dopamine Release

scholarly journals Depopulation of α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson’s disease model

2018 ◽  
Author(s):  
Michal Wegrzynowicz ◽  
Dana Bar-On ◽  
Laura Calo’ ◽  
Oleg Anichtchik ◽  
Mariangela Iovino ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Dopaminergic Neurons ◽  
Dopamine Release ◽  
Striatal Dopamine ◽  
Substantia Nigra Pars Compacta ◽  
Motor Deficit ◽  
Promising Therapeutic Approach ◽  
Striatal Dopamine Release

SUMMARYParkinson’s Disease (PD) is characterized by the presence of α-synuclein aggregates known as Lewy bodies and Lewy neurites, whose formation is linked to disease development. The causal relation between α-synuclein aggregates and PD is not well understood. We generated a new transgenic mouse line (MI2) expressing human, aggregation-prone truncated 1-120 α-synuclein under the control of the tyrosine hydroxylase promoter. MI2 mice exhibit progressive aggregation of α-synuclein in dopaminergic neurons of the substantia nigra pars compacta and their striatal terminals. This is associated with a progressive reduction of striatal dopamine release, reduced striatal innervation and significant nigral dopaminergic nerve cell death starting from 6 and 12 months of age, respectively. Overt impairment in motor behavior was found in MI2 mice at 20 months of age, when 50% of dopaminergic neurons are lost. These changes were associated with an increase in the number and density of 20-500nm α-synuclein species as shown by dSTORM. Treatment with the oligomer modulator anle138b, from 9-12 months of age, restored striatal dopamine release and prevented dopaminergic cell death. These effects were associated with a reduction of the inner density of α-synuclein aggregates and an increase in dispersed small α-synuclein species as revealed by dSTORM. The MI2 mouse model recapitulates the progressive dopaminergic deficit observed in PD, showing that early synaptic dysfunction precedes dopaminergic axonal loss and neuronal death that become associated with a motor deficit upon reaching a certain threshold. Our data also provide new mechanistic insight for the effect of anle138b’s function in vivo supporting that targeting α-synuclein aggregation is a promising therapeutic approach for PD.

Stimulation of the Subthalamic Nucleus in Parkinson's Disease Does Not Produce Striatal Dopamine Release

Neurosurgery ◽  
2003 ◽  
Vol 53 (5) ◽  
pp. 1095-1105 ◽  
Author(s):  
Aviva Abosch ◽  
Shitij Kapur ◽  
Anthony E. Lang ◽  
Doug Hussey ◽  
Elspeth Sime ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine Release ◽  
Rating Scale ◽  
Striatal Dopamine ◽  
Striatal Dopamine Release ◽  
Before And After ◽  
Disease Rating ◽  
The Right ◽  
Stimulation Of

Abstract OBJECTIVE The subthalamic nucleus (STN) is a target in the surgical treatment of Parkinson's disease (PD). The mechanism by which electrical stimulation of the STN ameliorates symptoms of PD remains unknown. One consistent aspect of STN stimulation is the ability to reduce the dosage of dopaminergic medications; sometimes they can be eliminated altogether. Furthermore, nigrostriatal projection axons are apposed to the dorsal surface of the STN and are likely affected by the application of current in this region. We sought to determine whether STN stimulation could release endogenous striatal dopamine. METHODS Five patients with PD, who had previously undergone surgical implantation of bilateral STN stimulators, underwent [11C]raclopride positron emission tomographic scanning. l-dopa was withheld for 12 hours, and both stimulators were turned off 9 hours before scanning. We assayed for striatal dopamine release by measuring radioligand displacement as a consequence of turning on the right STN stimulator after 45 minutes of a 90-minute [11C]raclopride infusion. Patients were evaluated with the motor section of the Unified Parkinson's Disease Rating Scale before and after the studies. RESULTS Comparisons between the right and left striata, before and after right STN stimulation, demonstrated no significant differences in [11C]raclopride binding, despite significant improvements in Unified Parkinson's Disease Rating Scale motor scores with unilateral stimulation (mean improvement, 26.0 ± 16.4%; P < 0.05). This finding was also noted when the striatum was partitioned into dorsal and ventral caudate and putamen and the four regions were analyzed separately. CONCLUSION Our results suggest that STN stimulation does not mediate its anti-PD effects via the release of dopamine, as assessed with [11C]raclopride displacement.

scholarly journals Stimulation of the Subthalamic Nucleus in Parkinson's Disease Does Not Produce Striatal Dopamine Release

Neurosurgery ◽  
2005 ◽  
Vol 56 (3) ◽  
pp. E629-E629
Author(s):  
Aviva Abosch ◽  
Shitij Kapur ◽  
Anthony E. Lang ◽  
Doug Hussey ◽  
Elspeth Sime ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Subthalamic Nucleus ◽  
Dopamine Release ◽  
Striatal Dopamine ◽  
Striatal Dopamine Release ◽  
Stimulation Of

scholarly journals Reduced striatal dopamine release during motor skill acquisition in Parkinson’s disease

PLoS ONE ◽  
2018 ◽  
Vol 13 (5) ◽  
pp. e0196661 ◽  
Author(s):  
Shoji Kawashima ◽  
Yoshino Ueki ◽  
Takashi Kato ◽  
Kengo Ito ◽  
Noriyuki Matsukawa
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Skill Acquisition ◽  
Motor Skill ◽  
Dopamine Release ◽  
Striatal Dopamine ◽  
Motor Skill Acquisition ◽  
Striatal Dopamine Release

Clozapine for the treatment of levodopa-induced psychosis and dyskinesia in Parkinson's disease

1994 ◽  
Vol 11 (2) ◽  
pp. 83-88 ◽  
Author(s):  
Isabelle Jalenques ◽  
André-Julien Coudert
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Low Dose ◽  
Dose Range ◽  
D2 Receptors ◽  
Striatal Dopamine ◽  
Clozapine Treatment ◽  
Length Of Treatment ◽  
Striatal Dopamine Release ◽  
Off Time

AbstractThe treatment of psychosis in patients with Parkinson's disease (PD) is one of the most difficult problems in clinical psychiatry. Clozapine's low propensity to induce extrapyramidal side effects makes it an attractive treatment for psychotic patients with PD. A number of published uncontrolled studies suggest that low-dose clozapine is effective in these patients. However, the dose range, side effect profiles and length of treatment have varied in these reports. In this article, the authors review the literature and report on the effects of clozapine in a patient with Parkinson's disease and psychosis. Clozapine (50mg per day) resulted in a complete resolution of psychosis, improvement of motor function, reduction of “off” time and a major improvement in levodopa-induced dystonic dyskinesias. The only adverse effect was mild sedation during the first two weeks of clozapine treatment. The lack of acute blockade of striatal D2 receptors by clozapine and the failure of chronic clozapine treatment to suppress striatal dopamine release may account for its beneficial effect in Parkinson's disease. Additionally, an ameliorating effect of clozapine on parkinsonism might be due to its action on serotonergic systems leading to release of striatal dopamine.

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