Menopause is associated with
memory deficits attributed to reduced serum
estrogen levels. We evaluated whether an increase in
brain-derived neurotrophic factor (
BDNF) and
nerve-growth factor (
NGF) levels, through
transplantation of
choline acetyltransferase (ChAT)-overexpressing neural stem cells (F3.ChAT), improved learning and memory in ovariectomized rats. PD13 mouse neuronal primary culture cells were treated with
estradiol or co-cultured with F3.ChAT cells;
choline transporter1 (CHT1), ChAT, and
vesicular acetylcholine transporter (VAChT) expression was evaluated using real-time PCR. The relationship between
estrogen receptors (ERs) and
neurotrophin family members was analyzed using immunohistochemistry. After the
transplantation of F3.ChAT cells into OVx rats, we evaluated the memory, ACh level, and the expression of ER,
neurotrophin family
proteins, and
cholinergic system.
Estradiol upregulated CHT1, ChAT, and VAChT expression in ER; they were co-localized with
BDNF,
NGF, and TrkB. Co-culture with F3.ChAT upregulated CHT1, ChAT, and VAChT by activating the
neurotrophin signalling pathway.
Transplantation of F3.ChAT cells in OVX animals increased the ACh level in the CSF and improved
memory deficit. In addition, it increased the expression of ERs,
neurotrophin signaling, and the
cholinergic system in the brains of OVX animals. Therefore, the
estradiol deficiency induced
memory loss by the down-regulation of the
neurotrophin family and F3.ChAT could ameliorate the
cognitive impairment owing to the loss or reduction of
estradiol.