Improvement of Cognitive Function in Ovariectomized Rats by Human Neural Stem Cells Overexpressing Choline Acetyltransferase via Secretion of NGF and BDNF

Abstract

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.

Improvement of Cognitive Function by Fermented Panax ginseng C.A. Meyer Berries Extracts in an AF64A-Induced Memory Deficit Model

“…However, treatment with post-fermented GBE counteracted the effect of AF64A, enhancing the activity of the cholinergic nervous system. This increase in activity was attributed to increased expression of NGF and BDNF, which prevent nerve cell death and promote their proliferation, as well as increased activity of the cholinergic nervous system [12,[53][54][55]. Thus, an increase in ginsenosides, such as Rg3, Rg5, and Rk1, in postfermented GBE seems to inhibit inflammation caused by AF64A and increase antioxidant effects to protect cells [56,57], as well as increase BDNF and NGF to regulate the expression of the cholinergic nervous system [58][59][60].…”

The effects of treadmill exercise on brain angiogenesis in ovariectomized rats

“…Our previous study has demonstrated the association between estrogen deficiency and cognitive dysfunction, particularly memory loss. (Yoon et al, 2021(Yoon et al, , 2022. Angiogenesis-related factors have been proposed as potential candidates for restoring vascular function and alleviating these symptoms.…”

The Neuroprotective Effects of Exosomes Derived from TSG101-Overexpressing Human Neural Stem Cells in a Stroke Model

“…The concentration of exosomes were measured by size, particle number, and exosome markers [ 24 ]. Especially, in the coculture with TSG101 cells, since exosomes are smaller than 0.4 μm, only exosomes were secreted at the 0.4 μm membrane, and at the 4.0 μm membrane, cells and exosomes affected N2A cells together [ 25 , 26 ]. These results were consistent with those obtained in N2A cells subjected to OGD and in the brain after MCAO.…”