Abstract
Background
Cerebral ischemia leads to linguistic and motor dysfunction, as the death of neurons in ischemic core is permanent and non-renewable. An innovative avenue is to induce and/or facilitate reprogramming of adjacent astrocytes into neurons to replace the lost neurons and re-establish brain homeostasis.
Purpose
This study aimed to investigate whether the p-hydroxy benzaldehyde (p-HBA), a phenolic compound isolated from Gastrodia elata Blume, could facilitate the reprogramming of oxygen-glucose deprivation/reperfusion (OGD/R)-damaged astrocytes into neurons.
Study Design/Methods
The primary parenchymal astrocytes of rat were exposure to OGD and reperfusion with define culture medium. Cells were then incubated with different concentration of p-HBA (1, 10, 100, 400 μM) and collected at desired time point for reprogramming process analysis.
Results
OGD/R could elicit endogenous neurogenic program in primary parenchymal astrocytes of rat under define culture condition, and these so-called reactive astrocytes could be reprogrammed into neurons. However, the neonatal neurons produced by this endogenous procedure could not develop into mature neurons, and the conversion rate was only 1.9%. Treatment of these reactive astrocytes with p-HBA could successfully promote the conversion rate to 6.1%, and the neonatal neurons could develop into mature neurons within 14 days. Further analysis showed that p-HBA down-regulated the Notch signal component genes Dll1, Hes1 and SOX2, while the transcription factor NeuroD1 was up-regulated.
Conclusion
The results of this study demonstrated that p-HBA facilitated the astrocyte-to-neuron conversion. This chemical reprogramming was mediated by inhibition of Notch1 signaling pathway and transcriptional activation of NeuroD1.
Acknowledgements
We are thankful for all the individuals who participated in the original studies. The content is solely the responsibility of the authors.
Availability of data and materials
All data generated or analysed during this study are included in this published article.
Ethics approval and consent to participate
The experiments were approved by the Animal Experiment Ethics Committee of Yunnan University of Chinese Medicine and were also conducted according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals.
Consent for publication
Not applicable.
Declaration of interest statement
The authors declare that they have no conflict of interest.
Author contributions
All authors took part in the study and take responsibility for the data analysis. Research idea and design: NZ. Experimental performance: XL, YY, XM, interpretation of data: JX. Writing and revising of the manuscript: RF, JX, NZ. Statistical analysis: RF, JX. Study supervision: NZ. All authors reviewed and approved the manuscript.
Disclosure statement
No potential conflict of interest was reported by the author(s).