title: Enhanced glutamatergic phenotype of mesencephalic dopamine neurons after neonatal 6-hydroxydopamine lesion.
abstract: There is increasing evidence that a subset of midbrain dopamine (DA) neurons uses glutamate as a co-transmitter and expresses vesicular glutamate transporter (VGLUT) 2, one of the three vesicular glutamate transporters. In the present study, double in situ hybridization was used to examine tyrosine hydroxylase (TH) and VGLUT2 mRNA expression during the embryonic development of these neurons, and postnatally, in normal rats and rats injected with 6-hydroxydopamine (6-OHDA) at P4 to destroy partially DA neurons. At embryonic days 15 and 16, there was a regional overlap in the labeling of TH and VGLUT2 mRNA in the ventral mesencephalon, which was no longer found at late embryonic stages (E18-E21) and postnatally. In normal pups from P5 to P15, only 1-2% of neurons containing TH mRNA in the ventral tegmental area (VTA) and substantia nigra, pars compacta, also displayed VGLUT2 mRNA. In contrast, after the cerebroventricular administration of 6-OHDA at P4, 26% of surviving DA neurons in the VTA of P15 rats expressed VGLUT2. To search for a colocalization of TH and VGLUT2 protein in axon terminals of these neurons, the nucleus accumbens of normal and 6-OHDA-lesioned P15 rats was examined by electron microscopy after dual immunocytochemical labeling. In normal rats, VGLUT2 protein was found in 28% of TH positive axon terminals in the core of nucleus accumbens. In 6-OHDA-lesioned rats, the total number of TH positive terminals was considerably reduced, and yet the proportion also displaying VGLUT2 immunoreactivity was modestly but significantly increased (37%). These results lead to the suggestion that the glutamatergic phenotype of a VTA DA neurons is highly plastic, repressed toward the end of normal embryonic development, and derepressed postnatally following injury. They also support the hypothesis of co-release of glutamate and DA by mesencephalic neurons in vivo, at least in the developing brain.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, QC, Canada H3C 3J7.
authors.forename: G
authors.initials: G
authors.lastname: Dal Bo
authors.forename: N
authors.initials: N
authors.lastname: Bérubé-Carrière
authors.forename: J A
authors.initials: JA
authors.lastname: Mendez
authors.forename: D
authors.initials: D
authors.lastname: Leo
authors.forename: M
authors.initials: M
authors.lastname: Riad
authors.forename: L
authors.initials: L
authors.lastname: Descarries
authors.forename: D
authors.initials: D
authors.lastname: Lévesque
authors.forename: L-E
authors.initials: LE
authors.lastname: Trudeau
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013565:Sympatholytics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D017557:Ventral Tegmental Area / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics
chemical_list: D012333:RNA, Messenger; C493475:Slc17a6 protein, rat; D013565:Sympatholytics; D050599:Vesicular Glutamate Transport Protein 2; D018698:Glutamic Acid; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine