title: Distinct effects of pramipexole on the proliferation of adult mouse sub-ventricular zone-derived cells and the appearance of a neuronal phenotype.
abstract: Pramipexole (PPX) is a dopamine agonist with an 8-fold higher affinity for D3 than D2 receptor, whose efficacy in the treatment of Parkinson's disease is based on dopamine agonistic activity. PPX has also been recently shown to be endowed with neuroprotective activity and neurogenic potential. The aim of this study was a more detailed characterization of PPX-induced neurogenesis. Both D2 and D3 receptors are expressed in floating and differentiated neurospheres obtained from the sub-ventricular zone (SVZ) of adult mice. Treatment of secondary neurospheres with 10 μM PPX causes a marked induction of cell proliferation, assessed by enhanced cell number and S phase population at cell cycle analysis. Stimulation of proliferation by PPX is still detectable in plated neurospheres before the onset of migration and differentiation, as by enhanced BrdU incorporation. This effect is sensitive to the selective D3 dopamine receptor antagonist U99194A, as well as to sulpiride. A 24 h treatment with PPX does not modify the morphology of neurosphere-derived cells, but causes an increase of glial fibrillary acidic protein (GFAP)-positive cells, an effect sensitive to both D2 and D3 antagonism. Differentiation toward the neuronal lineage is increased by PPX as shown by enhancement of the cell population positive to the early neuronal marker doublecortin (DCX) at 24 h and the mature neuronal marker microtubule associated protein (MAP2) at 72 h. This effect is not modified by treatment with U99194A and is mimicked by BDNF. Accordingly, PPX increases BDNF release with a mechanism involving D2 but not D3 receptors.
authors.affiliation: Department of Experimental and Clinical Pharmacology, University of Catania, Catania, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Merlo
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Canonico
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Sortino
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D018491:Dopamine Agonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007189:Indans / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D000077487:Pramipexole; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000096:biosynthesis; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D052160:Benzothiazoles; D019208:Brain-Derived Neurotrophic Factor; C000714847:Dcx protein, mouse; D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D007189:Indans; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C086335:(5,6-dimethoxyindan-2-yl)dipropylamine; D013469:Sulpiride; D000077487:Pramipexole