title: Striatal vessels receive phosphorylated tyrosine hydroxylase-rich innervation from midbrain dopaminergic neurons.
abstract: Nowadays it is assumed that besides its roles in neuronal processing, dopamine (DA) is also involved in the regulation of cerebral blood flow. However, studies on the hemodynamic actions of DA have been mainly focused on the cerebral cortex, but the possibility that vessels in deeper brain structures receive dopaminergic axons and the origin of these axons have not been investigated. Bearing in mind the evidence of changes in the blood flow of basal ganglia in Parkinson's disease (PD), and the pivotal role of the dopaminergic mesostriatal pathway in the pathophysiology of this disease, here we studied whether striatal vessels receive inputs from midbrain dopaminergic neurons. The injection of an anterograde neuronal tracer in combination with immunohistochemistry for dopaminergic, vascular and astroglial markers, and dopaminergic lesions, revealed that midbrain dopaminergic axons are in close apposition to striatal vessels and perivascular astrocytes. These axons form dense perivascular plexuses restricted to striatal regions in rats and monkeys. Interestingly, they are intensely immunoreactive for tyrosine hydroxylase (TH) phosphorylated at Ser19 and Ser40 residues. The presence of phosphorylated TH in vessel terminals indicates they are probably the main source of basal TH activity in the striatum, and that after activation of midbrain dopaminergic neurons, DA release onto vessels precedes that onto neurons. Furthermore, the relative weight of this "vascular component" within the mesostriatal pathway suggests that it plays a relevant role in the pathophysiology of PD.
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of La Laguna La Laguna, Tenerife, Spain ; Biomedical Technologies Institute (ITB, CIBICAN) La Laguna, Tenerife, Spain ; Spanish Network of Neurodegenerative Diseases (CIBERNED) Madrid, Spain.
authors.forename: Domingo
authors.initials: D
authors.lastname: Afonso-Oramas
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of La Laguna La Laguna, Tenerife, Spain ; Biomedical Technologies Institute (ITB, CIBICAN) La Laguna, Tenerife, Spain ; Spanish Network of Neurodegenerative Diseases (CIBERNED) Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Cruz-Muros
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of La Laguna La Laguna, Tenerife, Spain ; Biomedical Technologies Institute (ITB, CIBICAN) La Laguna, Tenerife, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Castro-Hernández
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of La Laguna La Laguna, Tenerife, Spain ; Spanish Network of Neurodegenerative Diseases (CIBERNED) Madrid, Spain.
authors.forename: Josmar
authors.initials: J
authors.lastname: Salas-Hernández
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of La Laguna La Laguna, Tenerife, Spain ; Biomedical Technologies Institute (ITB, CIBICAN) La Laguna, Tenerife, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Barroso-Chinea
authors.affiliation: Department of Pathology, University Hospital of Canary Islands Tenerife, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: García-Hernández
authors.affiliation: Spanish Network of Neurodegenerative Diseases (CIBERNED) Madrid, Spain ; Center for Applied Medical Research (CIMA), University of Navarra Pamplona, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Lanciego
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of La Laguna La Laguna, Tenerife, Spain ; Biomedical Technologies Institute (ITB, CIBICAN) La Laguna, Tenerife, Spain ; Spanish Network of Neurodegenerative Diseases (CIBERNED) Madrid, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: González-Hernández
keywords: Parkinson’s disease; Ser 19; Ser 40; cerebral blood flow; dopamine; midbrain; striatum