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Midbrain Gene Screening Identifies a New Mesoaccumbal Glutamatergic Pathway and a Marker for Dopamine Cells Neuroprotected in Parkinson's Disease
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Oramacell, F-75006 Paris, France..
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology. Univ Melbourne, Dept Anat & Neurosci, Melbourne, Vic 3010, Australia..
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 35203Article in journal (Refereed) Published
Abstract [en]

The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) of the midbrain are associated with Parkinson's disease (PD), schizophrenia, mood disorders and addiction. Based on the recently unraveled heterogeneity within the VTA and SNc, where glutamate, GABA and co-releasing neurons have been found to co-exist with the classical dopamine neurons, there is a compelling need for identification of gene expression patterns that represent this heterogeneity and that are of value for development of human therapies. Here, several unique gene expression patterns were identified in the mouse midbrain of which NeuroD6 and Grp were expressed within different dopaminergic subpopulations of the VTA, and TrpV1 within a small heterogeneous population. Optogenetics-coupled in vivo amperometry revealed a previously unknown glutamatergic mesoaccumbal pathway characterized by TrpV1-Cre-expression. Human GRP was strongly detected in non-melanized dopaminergic neurons within the SNc of both control and PD brains, suggesting GRP as a marker for neuroprotected neurons in PD. This study thus unravels markers for distinct subpopulations of neurons within the mouse and human midbrain, defines unique anatomical subregions within the VTA and exposes an entirely new glutamatergic pathway. Finally, both TRPV1 and GRP are implied in midbrain physiology of importance to neurological and neuropsychiatric disorders.

Place, publisher, year, edition, pages
2016. Vol. 6, 35203
National Category
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-307529DOI: 10.1038/srep35203ISI: 000385768100001PubMedID: 27762319OAI: oai:DiVA.org:uu-307529DiVA: diva2:1047474
Funder
Swedish Research Council, 2013-4657 2014-3804The Swedish Brain FoundationÅke Wiberg Foundation
Available from: 2016-11-17 Created: 2016-11-17 Last updated: 2016-11-17Bibliographically approved

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Viereckel, ThomasVlcek, BiancaBimpisidis, ZisisLagerström, Malin C.Konradsson-Geuken, ÅsaWallén-Mackenzie, Åsa
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