In vivo release of DOPA and dopamine from genetically engineered cells grafted to the denervated rat striatum

doi:10.1016/0896-6273(90)90078-T

Neuron

Volume 5, Issue 4, October 1990, Pages 393-402

https://doi.org/10.1016/0896-6273(90)90078-T Get rights and content

Abstract

Fibroblastic 3T3 and endocrine RIN cells were genetically modified by infection with a recombinant retrovirus encoding the form 1 of human tyrosine hydroxylase (TH) and selection in tyrosine-free medium. These cells were grafted to rats unilaterally lesioned with 6-hydroxydopamine. Both cell types survived implantation into the striatum, expressed TH immunoreactivity, and as assessed by microdialysis 8–9 days after implantation, secreted high amounts of DOPA and/or dopamine into the surrounding host striatum. The modified 3T3 cells secreted large amounts of DOPA that was efficiently decarboxylated to dopamine by the host striatal tissue; the newly synthesized dopamine was stored only to a limited extent in the denervated striatum. The modified RIN cells synthesized dopamine that was stored intracellularly and released in a regulated fashion. The grafted DOPA-secreting cells produced 4–5 times higher extracellular dopamine levels than the dopamine-secreting cells, and they were more efficient in reducing apomorphine-induced rotation. No effect was observed with either cell type on amphetamine-induced turning behavior.

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Neuron

In vivo release of DOPA and dopamine from genetically engineered cells grafted to the denervated rat striatum

Abstract

Brain Res.

Brain Res.

Exp. Neurol.

Brain Res.

Neuroscience

Brain Res.

Life Sci.

Neuroscience

Neuroscience

Neurosci. Lett.

Brain Res.

Exp. Neurol.

Brain Res.

Cyclosporin A increases survival of cross-species intrastriatal grafts of embryonic dopamine-containing neurons

Exp. Brain Res.

Intracerebral grafting of dopamine neurons

Ann. NY Acad. Sci.

Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: immunological aspects, spontaneous and drug-induced behaviour, and dopamine release

Exp. Brain Res.

Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: ultrastructural evidence for synapse formation using tyrosine hydroxylase immunocytochemistry

Exp. Brain Res.

Differentiation of the dopamine mechanisms mediating stereotyped behaviour and hyperactivity in the nucleus accumbens and caudate-putamen

J. Pharm. Pharmacol.

Effect of prior dopamine denervation on survival and fiber outgrowth from intrastriatal fetal mesencephalic grafts

Eur. J. Neurosci.