scholarly journals Allosteric modulation of GluN2C/GluN2D-containing NMDA receptors bidirectionally modulates dopamine release: implication for Parkinson's disease

2014 ◽  
Vol 171 (16) ◽  
pp. 3938-3945 ◽  
Author(s):  
X Zhang ◽  
Z-J Feng ◽  
K Chergui
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nmda Receptors ◽  
Dopamine Release ◽  
Allosteric Modulation

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.

Endogenous dopamine release during sequential movement in healthy volunteers and patients with Parkinson's disease: a PET study

NeuroImage ◽  
2001 ◽  
Vol 13 (6) ◽  
pp. 1172
Author(s):  
Ines K. Goerendt ◽  
Cristina Messa ◽  
Andrew D. Lawrence ◽  
Paola Piccini ◽  
Paul M. Grasby ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Healthy Volunteers ◽  
Dopamine Release ◽  
Endogenous Dopamine ◽  
Sequential Movement ◽  
Endogenous Dopamine Release
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