Gintonin stimulates dendritic growth in striatal neurons by activating Akt and CREB

Hye Kyung Lim; Kitaek Kim; Youn Kyoung Son; Seung-Yeol Nah; Soo Min Ahn; Minseok Song

doi:10.3389/fnmol.2022.1014497

Gintonin stimulates dendritic growth in striatal neurons by activating Akt and CREB

Front Mol Neurosci. 2022 Oct 26:15:1014497. doi: 10.3389/fnmol.2022.1014497. eCollection 2022.

Authors

Hye Kyung Lim¹, Kitaek Kim¹, Youn Kyoung Son², Seung-Yeol Nah³, Soo Min Ahn⁴, Minseok Song¹

Affiliations

¹ Department of Life Sciences, Yeungnam University, Gyeongsan, South Korea.
² National Institute of Biological Resources, Incheon, South Korea.
³ Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, South Korea.
⁴ Department of Pediatric Surgery, Metabolic and Bariatric Surgery Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.

Abstract

Gintonin, a glycolipid protein conjugated with lysophosphatidic acid (LPA), is a newly identified compound extracted from Korean ginseng. LPA receptor isotypes exhibit high affinity for gintonin and mediate intracellular calcium signaling in various animal cell models. In this study, we found that gintonin induced the activation of Akt and cAMP-response element binding protein (CREB) in mouse striatal neurons, and chronic treatment with gintonin potently induced dendritic growth and filopodia formation. Gintonin-induced Akt/CREB activation and dendritic development were significantly impaired by LPA receptor (LPAR1/3) inhibition with Ki16425. Intriguingly, prolonged treatment with gintonin ameliorated the reduction in dendritic formation caused by Shank3 and Slitrk5 deficiency in the striatal neurons. In addition, gintonin and brain-derived neurotrophic factor (BDNF) had a synergistic effect on AKT/CREB activation and dendritic growth at suboptimal concentrations. These findings imply that gintonin-stimulated LPA receptors play a role in dendritic growth in striatal neurons and that they may act synergistically with BDNF, which is known to play a role in dendritogenesis.

Keywords: BDNF; LPA; dendritic growth; gintonin; striatal neurons.