Parkinson's disease: Mechanisms and models

Schultz, Wolfram. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80: 1–27, 1998. The effects of lesions, receptor blocking, electrical self-stimulation, and drugs of abuse suggest t...

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Predictive Reward Signal of Dopamine Neurons

Missale, Cristina, S. Russel Nash, Susan W. Robinson, Mohamed Jaber, and Marc G. Caron. Dopamine Receptors: From Structure to Function. Physiol. Rev. 78: 189–225, 1998. — The diverse physiological actions of dopamine are mediated by at least five distinct G protein-coupled receptor subtypes. Two D1-like receptor subtypes (D1 and D5) couple to the G protein Gs and activate adenylyl cyclase. The other receptor subtypes belong to the D2-like subfamily (D2 , D3 , and D4) and are prototypic of G protein-coupled receptors that inhibit adenylyl cyclase and activate K+ channels. The genes for the D1 and D5 receptors are intronless, but pseudogenes of the D5 exist. The D2 and D3 receptors vary in certain tissues and species as a result of alternative splicing, and the human D4 receptor gene exhibits extensive polymorphic variation. In the central nervous system, dopamine receptors are widely expressed because they are involved in the control of locomotion, cognition, emotion, and affect as well as neuroendocrine s...

Dopamine Receptors: From Structure to Function

http://www.back-in-business-physiotherapy.com/images/files/DescendingControl.pdf

Descending control of pain.

http://www.columbia.edu/itc/gsas/g9600/2003/JavitchReadings/Schultz(Sulzer).pdf

Getting Formal with Dopamine and Reward

A recombinant rodent comprises cells containing a pair of genomic dopamine transporter protein alleles, wherein at least one of said alleles is incapable of expressing endogenous dopamine transporter protein. The rodent may be a homozygote, where both of said alleles are incapable of expressing endogenous dopamine transporter protein, or the rodent may be a heterozygote, and one of said alleles expresses endogenous dopamine transporter protein. The rodent is preferably a mouse.

Dopamine transporter knockout mice

Effect of reserpine treatment on enkephalin mRNA level in the rat striatum: an in situ hybridization study

Intrastriatal embryonic ventral mesencephalon grafts have been shown to integrate, survive, and reinnervate the host striatum in clinical settings and in animal models of Parkinson’s disease. However, this ectopic location does not restore the physiological loops of the nigrostriatal pathway and promotes only moderate behavioral benefits. Here, we performed a direct comparison of the potential benefits of intranigral versus intrastriatal grafts in animal models of Parkinson’s disease. We report that intranigral grafts promoted better survival of dopaminergic neurons and that only intranigral grafts induced recovery of fine motor skills and normalized cortico-striatal responses. The increase in the number of toxic activated glial cells in host tissue surrounding the intrastriatal graft, as well as within the graft, may be one of the causes of the increased cell death observed in the intrastriatal graft. Homotopic localization of the graft and the subsequent physiological cell rewiring of the basal ganglia may be a key factor in successful and beneficial cell transplantation procedures.

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Better Outcomes with Intranigral versus Intrastriatal Cell Transplantation: Relevance for Parkinson’s Disease

Nous avons recemment obtenu, par recombinaison homologue, des souris transgeniques n'exprimant pas le gene du transporteur de la dopamine (DAT). Ces souris ont une hyperactivite locomotrice spontanee, qui reflete une hyperdopaminergie aussi elevee que chez des souris normales traitees a des fortes doses de cocaine. Paradoxalement, il existe une baisse de 90 % de la dopamine intracellulaire chez ces animaux alors que la dopamine liberee persiste 300 fois plus longtemps dans le milieu extracellulaire que chez des souris normales. Les niveaux de l'enzyme cle dans la biosynthese de dopamine, sont de 10 % par rapport a des souris normales, en accord avec les niveaux de dopamine. De plus, dans ce modele animal, il s'est avere que la tyrosine hydroxylase (TH) est regulee au niveau de la transcription, de la traduction, de son activite et de son adressage. Nos resultats montrent la part cruciale du transporteur de la dopamine dans le controle du tonus dopaminergique et etablissent son role dans les consequences biochimiques et comportementales de l'action de l'amphetamine, de la cocaine et de la morphine. De plus, l'etude de ces souris transgeniques promet d'aboutir a des applications cliniques et sociales concernant notamment la maladie de Parkinson, l'hyperkinesie et la dependance aux psychostimulants.

Mohamed Jaber

Papers

Dopamine transporter knockout mice

Effect of reserpine treatment on enkephalin mRNA level in the rat striatum: an in situ hybridization study

Better Outcomes with Intranigral versus Intrastriatal Cell Transplantation: Relevance for Parkinson’s Disease

[Behavioral, cellular and molecular consequences of the dopamine transporter gene inactivation].

Expression of polyadenylated and non-polyadenylated trkC transcripts in the rodent central nervous system.