Basal and Evoked Neurotransmitter Levels in Parkin, DJ-1, PINK1 and LRRK2 Knockout Rat Striatum.

Autor: Creed RB; Center for Neurodegeneration and Experimental Therapeutics, The University of Alabama at Birmingham, Birmingham, Alabama 35294; Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama 35294., Menalled L; The Michael J. Fox Foundation for Parkinson's Research, 111 West 33(rd) Street, 10(th) Floor, New York, NY 10001., Casey B; The Michael J. Fox Foundation for Parkinson's Research, 111 West 33(rd) Street, 10(th) Floor, New York, NY 10001., Dave KD; The Michael J. Fox Foundation for Parkinson's Research, 111 West 33(rd) Street, 10(th) Floor, New York, NY 10001., Janssens HB; Brains On-Line, 7000 Shoreline Court, South San Francisco, CA 94080., Veinbergs I; Brains On-Line, 7000 Shoreline Court, South San Francisco, CA 94080., van der Hart M; Brains On-Line, 7000 Shoreline Court, South San Francisco, CA 94080., Rassoulpour A; Brains On-Line, 7000 Shoreline Court, South San Francisco, CA 94080., Goldberg MS; Center for Neurodegeneration and Experimental Therapeutics, The University of Alabama at Birmingham, Birmingham, Alabama 35294; Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama 35294; Department of Neurobiology, The University of Alabama at Birmingham, Birmingham, Alabama 35294. Electronic address: mattgoldberg@uab.edu.
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2019 Jun 15; Vol. 409, pp. 169-179. Date of Electronic Publication: 2019 Apr 25.
DOI: 10.1016/j.neuroscience.2019.04.033
Abstrakt: Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the loss of neurons in the substantia nigra that project to the striatum and release dopamine (DA), which is required for normal movement. Common non-motor symptoms likely involve abnormalities with other neurotransmitters, such as serotonin, norepinephrine, acetylcholine, glycine, glutamate and gamma-aminobutyric acid (GABA). As part of a broad effort to provide better PD research tools, the Michael J. Fox Foundation for Parkinson's Research funded the generation and characterization of knockout (KO) rats for genes with PD-linked mutations, including PINK1, Parkin, DJ-1 and LRRK2. Here we extend the phenotypic characterization of these lines of KO rats to include in vivo microdialysis to measure both basal and potassium-induced release of the above neurotransmitters and their metabolites in the striatum of awake and freely moving rats at ages 4, 8 and 12 months compared to wild-type (WT) rats. We found age-dependent abnormalities in basal DA, glutamate and acetylcholine in PINK1 KO rats and age-dependent abnormalities in basal DA metabolites in Parkin and LRRK2 KO rats. Parkin KO rats had increased glycine release while DJ-1 KO rats had decreased glutamate release and increased acetylcholine release compared to WT rats. All lines except DJ-1 KO rats showed age-dependent changes in release of one or more neurotransmitters. Our data suggest these rats may be useful for studies of PD-related synaptic dysfunction and neurotransmitter dynamics as well as studies of the normal and pathogenic functions of these genes with PD-linked mutations.
(Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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