We previously showed that
gintonin, an exogenous
lysophosphatidic acid (
LPA) receptor ligand, attenuated β-
amyloid plaque formation in the cortex and hippocampus, and restored β-
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 (0.3 μg/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 β-
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.