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Tyrosine hydroxylase cells appearing in the mouse striatum after dopamine denervation are likely to be projection neurones regulated by l-DOPA

AuthorsDarmopil, Sanja ; Muñetón-Gómez, Vilma; Ceballos, María L. de ; Bernson, Miya; Moratalla, Rosario
Keywordsaromatic-L-amino acid decarboxylase
dopamine transporter
L-3, 4-dihydroxyphenylalanine
Parkinson's disease
Issue Date2008
PublisherJohn Wiley & Sons
CitationEuropean Journal of Neuroscience 27 (3): 580-592 (2008)
AbstractTyrosine hydroxylase (TH)-immunoreactive (ir) neurones are detected in the striatum of animals after dopamine depletion and also in human parkinsonian patients. Although there is extensive evidence for TH-ir neurones in the lesioned rodent striatum, there are few details regarding the molecular phenotype of these neurones, regulation of their TH expression after l-3,4-dihydroxyphenylalanine (L-DOPA) treatment and their function. In the present study, we examined the time-course of appearance of TH-ir neurones in the mouse striatum after 6-hydroxydopamine (6-OHDA) lesion and determined their molecular phenotype. We found that TH-ir neurones appeared in the striatum as early as 3 days after a 6-OHDA lesion. By 1 week after the lesion, the number of TH-ir neurones started to decrease and this decrease progressed significantly over time. Treatment with L-DOPA increased both the number of TH-ir neurones and the intensity of their immunolabelling. The TH-ir neurones that appear after the 6-OHDA lesion in the striatum are not newly generated cells as they did not incorporate 5-bromo-2-deoxyuridine. We found that the vast majority of TH-ir neurones colocalized with dynorphin and enkephalin, suggesting that they are projection neurones of the direct and indirect striatal output pathways. TH-ir neurones did not express the dopamine transporter but half of them expressed amino acid decarboxylase, an enzyme required for dopamine synthesis. Finally, striatal TH-ir neurones are functionally active, expressing the neuronal activation marker FosB in response to L-DOPA treatment. Promotion of these striatal TH-ir neurones may be beneficial in Parkinson's disease, particularly in the early stages when dopamine denervation is incomplete.
Publisher version (URL)http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9568.2008.06040.x/pdf
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