Gintonin, a novel ginseng-derived
lysophosphatidic acid receptor ligand, improves brain functions and protects neurons from oxidative stress. However, little is known about the effects of
gintonin against Pb-induced brain maldevelopment. We investigated the protective effects of
gintonin on the developing cerebellum after prenatal and postnatal Pb exposure. Pregnant female rats were randomly divided into three groups: control, Pb (0.3% Pb
acetate in
drinking water), and Pb plus
gintonin (100 mg/kg, p.o.). Blood Pb was increased in dams and pups;
gintonin treatment significantly decreased blood Pb. On postnatal day 21, the number of degenerating Purkinje cells was remarkably increased while the number of
calbindin-, GAD67-, NMDAR1-, LPAR1-immunoreactive intact Purkinje cells, and
GABA transporter 1-immunoreactive pinceau structures were significantly reduced in Pb-exposed offspring. Following Pb exposure,
gintonin ameliorated cerebellar degenerative effects, restored increased pro-apoptotic Bax, and decreased anti-apoptotic Bcl2.
Gintonin treatment attenuated Pb-induced accumulation of oxidative stress (Nrf2 and
Mn-SOD) and
inflammation (IL-1β and TNFα,), restoring the decreased cerebellar
BDNF and
Sirt1.
Gintonin ameliorated Pb-induced impairment of
myelin basic protein-immunoreactive myelinated fibers of Purkinje cells.
Gintonin attenuated Pb-induced locomotor dysfunctions. The present study revealed the ameliorating effects of
gintonin against Pb, suggesting the potential use of
gintonin as a preventive agent in Pb
poisoning during pregnancy and lactation.