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6-hydroxydopamine-induced Parkinson's disease-like degeneration generates acute micro- and astrogliosis in the nigrostriatal system but no Bioluminescence Imaging detectable alteration in adult neurogenesis.

Fricke, Inga B; Viel, Thomas; Worlitzer, Maik M; Collmann, Franziska M; Vrachimis, Alexis; Faust, Andreas; Wachsmuth, Lydia; Faber, Cornelius; Dollé, Frédéric; Kuhlmann, Michael T; Schäfer, Klaus; Hermann, Sven; Schwamborn, Jens C; Jacobs, Andreas H

Parkinson’s disease (PD) 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 which 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 ([123I]Ioflupane SPECT, DaTscanTM) and neuroinflammation in SN and striatum ([18F]DPA-714 PET) in the intranigral 6-hydroxydopamine (6-OHDA) PD 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 (OB) axis via bioluminescence imaging (BLI) under disease and control conditions. We found that activation of microglia in the SN is an acute process coming along with the degeneration of dopaminergic cell bodies in the SN. Dopaminergic deafferentation of the striatum does not influence the generation of Dcx+ neuroblasts in the SVZ, but generates chronic astrogliosis in the nigrostriatal system.

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