Neural stem cells transplantation combined with ethyl stearate promotes the activation of quiescent NSCs and improves PD rats motor behavior

Abstract

Background: This research aimed to examine the impact of co-transplantation of ethyl stearate (PubChem CID: 8122) and neural stem cells (NSCs) on endogenous NSCs in Parkinson's disease (PD) model rats, and also determine the impact of ethyl stearate on quiescent neural stem cells (qNSCs) and explore its possible mechanism.

Methods: The induction of PD rats was achieved through the injection of 6-hydroxydopamine (6-OHDA) into the right striatum (STR) and substantia nigra (SN). Transplant treatment was then followed for 6 weeks in the right STR. Apomorphine (APO)-induced rotation behavior and the pole climbing test were used to assess the effects of transplant treatment in each group. Western blotting (WB) and immunofluorescence staining were used to observe changes in endogenous NSCs. The effect of ethyl stearate on qNSCs was examined in vitro, with detection of associated indicators achieved through WB, immunofluorescence, flow cytometry and qRT-PCR.

Results: Co-transplantation of NSCs with ethyl stearate significantly ameliorated motor deficits in PD rats and upregulated the expression of tyrosine hydroxylase (TH), Sox2, and Nestin. We established an in vitro system for NSC quiescence and activation. In qNSCs, ethyl stearate treatment increased Ki67 positivity and reduced the proportion of cells in the G0–G1 phase of the cell cycle, whereas withdrawal of ethyl stearate exerted the opposite effects. Ethyl stearate also downregulated EphB2 protein levels and upregulated p-AKT and CyclinD1 in qNSCs; these effects were reversed upon its removal.

Conclusion: These findings imply that co-transplantation of NSCs and ethyl stearate may help ameliorate motor impairment in PD rats by activating endogenous NSCs and promoting their development into dopaminergic neurons. Ethyl stearate may regulate the entry and exit of NSCs from quiescence through the EphB2/AKT/CyclinD1 pathway.

Keywords

EphB2/AKT/CyclinD1 pathway / ethyl stearate / neural stem cells / Parkinson's disease / quiescence

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