Articles

  • the Korean Society for Brain and Neural Sciences

Article

Original Article

Exp Neurobiol 2018; 27(2): 112-119

Published online April 30, 2018

https://doi.org/10.5607/en.2018.27.2.112

© The Korean Society for Brain and Neural Sciences

Aucubin Promotes Differentiation of Neural Precursor Cells into GABAergic Neurons

Miyeoun Song1, Hyomin Kim1, Sujin Park1, Hyockman Kwon3, Insil Joung4 and Yunhee Kim Kwon1,2*

1Department of Life and Nanopharmarceutical Science, Kyung Hee University, Seoul 02447, 2Department of Biology, Kyung Hee University, Seoul 02447, 3Department of Biosciences and Biotechnology, Hankuk University of Foreign Studies, Yongin 17035, 4Department of Biological Sciences, Hanseo University, Seosan 31962, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-961-0844, FAX: 82-2-966-4497
e-mail: kimyh@khu.ac.kr

Received: February 21, 2018; Revised: February 26, 2018; Accepted: February 28, 2018

Aucubin is a small compound naturally found in traditional medicinal herbs with primarily anti-inflammatory and protective effects. In the nervous system, aucubin is reported to be neuroprotective by enhancing neuronal survival and inhibiting apoptotic cell death in cultures and disease models. Our previous data, however, suggest that aucubin facilitates neurite elongation in cultured hippocampal neurons and axonal regrowth in regenerating sciatic nerves. Here, we investigated whether aucubin facilitates the differentiation of neural precursor cells (NPCs) into specific types of neurons. In NPCs cultured primarily from the rat embryonic hippocampus, aucubin significantly elevated the number of GAD65/67 immunoreactive cells and the expression of GAD65/67 proteins was upregulated dramatically by more than three-fold at relatively low concentrations of aucubin (0.01 µM to 10 µM). The expression of both NeuN and vGluT1 of NPCs, the markers for neurons and glutamatergic cells, respectively, and the number of vGluT1 immunoreactive cells also increased with higher concentrations of aucubin (1 µM and 10 µM), but the ratio of the increases was largely lower than GAD expression and GAD immunoreactive cells. The GABAergic differentiation of pax6-expressing late NPCs into GABA-producing cells was further supported in cortical NPCs primarily cultured from transgenic mouse brains, which express recombinant GFP under the control of pax6 promoter. The results suggest that aucubin can be developed as a therapeutic candidate for neurodegenerative disorders caused by the loss of inhibitory GABAergic neurons.

Graphical Abstract


Keywords: aucubin, primary neuronal precursor cells, neuronal differentiation, GABAergic neuron, glutamatergic neuron