Abstract

BACKGROUND: Alzheimer’s disease (AD) is the most common type of dementia. It causes progressive brain disorder involving loss of normal memory and thinking skills. The transplantation of neural stem cells (NSCs) has been reported to improve learning and memory function of AD rats, and protects basal forebrain cholinergic neurons. Nerve growth factor – poly (ethylene glycol) – poly (lactic-co-glycolic acid)-nanoparticles (NGF-PEG-PLGA-NPs) can facilitate the differentiation of NSCs in vitro. This study thus investigated the treatment efficacy of NGF-PEG-PLGA-NPs combining NSC transplantation in AD model rats.

MATERIAL AND METHODS: AD rats were prepared by injection of 192IgG-saporin into their lateral ventricles. Embryonic rat NSCs were separated, induced by NGF-PEG-PLGA-NPs in vitro, and were transplanted. The Morris water-maze test was used to evaluate learning and memory function, followed by immunohistochemical staining for basal forebrain cholinergic neurons, hippocampal synaptophysin, and acetylcholine esterase (AchE) fibers.

RESULTS: Rats in the combined treatment group had significantly improved spatial learning ability compared to AD model animals (p<0.05). The number of basal forebrain cholinergic neurons, hippocampal synaptophysin, and AchE-positive fibers were all significantly larger than in the NSC-transplantation group, with no difference from control animals.

CONCLUSIONS: NGF-PEG-PLGA-NPs plus NSC transplantation can significantly improve learning and memory functions of AD rats, replenish basal forebrain cholinergic neurons, and help form hippocampal synapses and AchE-positive fibers. These findings may offer practical support for and insight into treatment of Alzheimer’s disease.

Keywords: Alzheimer Disease - therapy, Basal Forebrain - physiopathology, Brain - physiopathology, Cholinergic Neurons - pathology, Hippocampus - metabolism, Learning, Memory, Nanoparticles - therapeutic use, Nerve Growth Factor - pharmacology, Neural Stem Cells - transplantation, Polyesters, Polyethylene Glycols