Kim, Hyeon-Joong Kim, Dae-Joong Shin, Eun-Ju Lee, Byung-Hwan Choi, Sun-Hye Hwang, Sung-Hee Rhim, Hyewhon Cho, Ik-Hyun Kim, Hyoung-Chun Nah, Seung-Yeol 2024-01-20T03:00:27Z 2024-01-20T03:00:27Z 2021-09-04 2016-12 0197-0186 https://pubs.kist.re.kr/handle/201004/123387 We previously showed that gintonin, an exogenous lysophosphatidic acid (LPA) receptor ligand, attenuated beta-amyloid plaque formation in the cortex and hippocampus, and restored beta-amyloid-induced memory dysfunction. Both endogenous LPA and LPA receptors play a key role in embryonic brain development. However, little is known about whether gintonin can induce hippocampal cell proliferation in adult wild-type mice and an APPswe/PSEN-1 double Tg mouse model of Alzheimer's disease (AD). In the present study, we examined the effects of gintonin on the proliferation of hippocampal neural progenitor cells (NPCs) in vitro and its effects on the hippocampal cell proliferation in wild-type mice and a transgenic AD mouse model. Gintonin treatment increased 5-bromo-2'-deoxyuridine (BrdU) incorporation in hippocampal NPCs in a dose- and time-dependent manner. Gintonin (03 mu g/ml) increased the immunostaining of glial fibrillary acidic protein, NeuN, and LPA1 receptor in hippocampal NPCs. However, the gintonin-induced increase in BrdU incorporation and immunostaining of biomarkers was blocked by an LPA1/3 receptor antagonist and Ca2+ chelator. Oral administration of the gintonin-enriched fraction (50 and 100 mg/kg) increased hippocampal BrdU incorporation and LPA1/3 receptor expression in adult wild-type and transgenic AD mice. The present study showed that gintonin could increase the number of hippocampal neurons in adult wild-type mice and a transgenic AD mouse model. Our results indicate that gintonin-mediated hippocampal cell proliferation contributes to the gintonin-mediated restorative effect against beta-amyloid-induced hippocampal dysfunction. These results support the use of gintonin for the prevention or treatment of neurodegenerative diseases such as AD via promotion of hippocampal neurogenesis. (C) 2016 Elsevier Ltd. All rights reserved. English PERGAMON-ELSEVIER SCIENCE LTD LYSOPHOSPHATIDIC ACID RECEPTOR BIOLOGICAL ACTIONS LPA RECEPTORS NEUROGENESIS GINSENG ACTIVATION INVOLVEMENT MEMORY ENHANCEMENT SYNAPSES Effects of gintonin-enriched fraction on hippocampal cell proliferation in wild-type mice and an APPswe/PSEN-1 double Tg mouse model of Alzheimer's disease Article 10.1016/j.neuint.2016.10.006 1 NEUROCHEMISTRY INTERNATIONAL, v.101, pp.56 - 65 NEUROCHEMISTRY INTERNATIONAL 101 56 65 scie scopus 000390079100007 2-s2.0-84992751842 Biochemistry & Molecular Biology Neurosciences Biochemistry & Molecular Biology Neurosciences & Neurology Article LYSOPHOSPHATIDIC ACID RECEPTOR BIOLOGICAL ACTIONS LPA RECEPTORS NEUROGENESIS GINSENG ACTIVATION INVOLVEMENT MEMORY ENHANCEMENT SYNAPSES Ginseng Gintonin LPA receptor Alzheimer&apos s disease Hippocampal neurogenesis