Endogenous Nerve Regeneration In Parkinson 's Disease Mice

Section Ⅰ:Transcriptome profiling of the subventricular zone and the dentate gyrus in a parkinsonian animal modelAdult neurogenesis in the subventricular zone (SVZ) as well as in the subgranular zone (SGZ) contributes to brain maintenance and regeneration. In the adult brain, dopamine (DA) can regulate the endogenous neural stem cells (NSCs) within these two regions, while DA deficit may affect neurogenesis. Notably, the factors that regulate in vivo neurogenesis in these subregions have not been fully characterized, particularly after DA depletion. Here we performed RNA-sequencing (RNA-Seq) to investigate transcriptomic changes in the SVZ and dentate gyrus (DG) of mice in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This analysis identified differential genes which were involved in regulation of transcription, immune response, extracellular region, cell junction, and myelination, etc. These genes partially displayed different temporal profiles of expression, some of which might participate in the metabolic switch related to neurogenesis. Additionally, the mitogen-activated protein kinase (MAPK) signaling pathway has been positively regulated in the SVZ, while negatively impacted in the DG after MPTP administration. Overall, our findings indicate that MPTP exposure may exert different influences on transcriptome profiling between the SVZ and DG.Section Ⅱ:Transplantation of Human Neural Stem Cells in a Parkinsonian Model Exerts Neuroprotection via Regulation of the Host MicroenvironmentParkinson’s disease (PD) is characterized by a progressive loss of dopaminergic neurons and consequent dopamine (DA) deficit, and current treatment still remains a challenge. Although neural stem cells (NSCs) have been evaluated as appealing graft sources, mechanisms underlying the beneficial phenomena are not well understood. Here, we investigate whether human NSCs (hNSCs) transplantation could provide neuroprotection against DA depletion by recruiting endogenous cells to establish a favorable niche. Adult mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were transplanted with hNSCs or vehicle into the striatum. Behavioral and histological analyses demonstrated significant neurorescue response observed in hNSCs-treated animals compared with the control mice.In transplanted animals, grafted cells survived, proliferated, and migrated within the astrocytic scaffold. Notably, more local astrocytes underwent de-differentiation, acquiring the properties of NSCs or neural precursor cells (NPCs) in mice given hNSCs. Additionally, we also detected significantly higher expression of host-derived growth factors in hNSCs-transplanted mice compared with the control animals, together with inhibition of local microglia and proinflammatory cytokines. Overall, our results indicate that hNSCs transplantation exerts neuroprotection in MPTP-insulted mice via regulating the host niche. Harnessing synergistic interaction between the grafts and host cells may help optimize cell-based therapies for PD.