title: 6-hydroxydopamine-induced Parkinson's disease-like degeneration generates acute microgliosis and astrogliosis in the nigrostriatal system but no bioluminescence imaging-detectable alteration in adult neurogenesis.
abstract: Parkinson's disease is a slowly progressing neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra (SN), leading to severe impairment in motor and non-motor functions. Endogenous subventricular zone (SVZ) neural stem cells constantly give birth to new cells that might serve as a possible source for regeneration in the adult brain. However, neurodegeneration is accompanied by neuroinflammation and dopamine depletion, potentially compromising regeneration. We therefore employed in vivo imaging methods to study striatal deafferentation (N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-[(123) I]iodophenyl)nortropane single photon emission computed tomography, DaTscan(™) ) and neuroinflammation in the SN and striatum (N,N-diethyl-2-(2-(4-(2-[(18) F]fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide positron emission tomography, [(18) F]DPA-714 PET) in the intranigral 6-hydroxydopamine Parkinson's disease mouse model. Additionally, we transduced cells in the SVZ with a lentivirus encoding firefly luciferase and followed migration of progenitor cells in the SVZ-olfactory bulb axis via bioluminescence imaging under disease and control conditions. We found that activation of microglia in the SN is an acute process accompanying the degeneration of dopaminergic cell bodies in the SN. Dopaminergic deafferentation of the striatum does not influence the generation of doublecortin-positive neuroblasts in the SVZ, but generates chronic astrogliosis in the nigrostriatal system.
authors.affiliation: European Institute for Molecular Imaging (EIMI), University of Münster, Waldeyerstraße 15, D-48149, Münster, Germany.|ZMBE, Institute of Cell Biology, Stem Cell Biology and Regeneration Group, University of Münster, Münster, Germany.
authors.forename: Inga B
authors.initials: IB
authors.lastname: Fricke
authors.affiliation: European Institute for Molecular Imaging (EIMI), University of Münster, Waldeyerstraße 15, D-48149, Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Viel
authors.affiliation: ZMBE, Institute of Cell Biology, Stem Cell Biology and Regeneration Group, University of Münster, Münster, Germany.
authors.forename: Maik M
authors.initials: MM
authors.lastname: Worlitzer
authors.affiliation: European Institute for Molecular Imaging (EIMI), University of Münster, Waldeyerstraße 15, D-48149, Münster, Germany.
authors.forename: Franziska M
authors.initials: FM
authors.lastname: Collmann
authors.affiliation: European Institute for Molecular Imaging (EIMI), University of Münster, Waldeyerstraße 15, D-48149, Münster, Germany.|Department of Nuclear Medicine, University Hospital Münster, Münster, Germany.
authors.forename: Alexis
authors.initials: A
authors.lastname: Vrachimis
authors.affiliation: European Institute for Molecular Imaging (EIMI), University of Münster, Waldeyerstraße 15, D-48149, Münster, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Faust
authors.affiliation: Department of Clinical Radiology, University Hospital Münster, Münster, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Wachsmuth
authors.affiliation: Department of Clinical Radiology, University Hospital Münster, Münster, Germany.|DFG EXC 1003, Cluster of Excellence 'Cells in Motion', Münster, Germany.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Faber
authors.affiliation: CEA, I2BM, Service Hospitalier Frédéric Joliot, Orsay, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.affiliation: European Institute for Molecular Imaging (EIMI), University of Münster, Waldeyerstraße 15, D-48149, Münster, Germany.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Kuhlmann
authors.affiliation: European Institute for Molecular Imaging (EIMI), University of Münster, Waldeyerstraße 15, D-48149, Münster, Germany.|DFG EXC 1003, Cluster of Excellence 'Cells in Motion', Münster, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schäfers
authors.affiliation: European Institute for Molecular Imaging (EIMI), University of Münster, Waldeyerstraße 15, D-48149, Münster, Germany.|DFG EXC 1003, Cluster of Excellence 'Cells in Motion', Münster, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hermann
authors.affiliation: ZMBE, Institute of Cell Biology, Stem Cell Biology and Regeneration Group, University of Münster, Münster, Germany.|Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Belval, Luxembourg.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Schwamborn
authors.affiliation: European Institute for Molecular Imaging (EIMI), University of Münster, Waldeyerstraße 15, D-48149, Münster, Germany.|DFG EXC 1003, Cluster of Excellence 'Cells in Motion', Münster, Germany.|Department of Geriatric Medicine, Evangelische Kliniken, Johanniter Krankenhaus, Bonn, Germany.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology; D049109:Cell Proliferation; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000473:pathology*; D004660:Encephalitis / Q000150:complications / Q000473:pathology*; D005911:Gliosis / Q000150:complications*; D057809:HEK293 Cells; D006801:Humans; D008163:Luminescent Measurements; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000473:pathology; D009434:Neural Pathways / Q000473:pathology / Q000502:physiology; D058953:Neural Stem Cells / Q000473:pathology / Q000502:physiology; D055495:Neurogenesis; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications / Q000473:pathology*; D049268:Positron-Emission Tomography; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology*
chemical_list: D016627:Oxidopamine
keywords: 6-hydroxydopamine; Parkinson's disease; [18F]DPA-714; mouse; neuroinflammation