Neural stem cell transplantation improves learning and memory by protecting cholinergic neurons and restoring synaptic impairment in an amyloid precursor protein/presenilin 1 transgenic mouse model of Alzheimer's disease

Zhu,Qing; Zhang,Nianping; Hu,Nan; Jiang,Rongrong; Lu,Huicong; Xuan,Aiguo; Long,Dahong; Chen,Yan

doi:10.3892/mmr.2020.10918

Neural stem cell transplantation improves learning and memory by protecting cholinergic neurons and restoring synaptic impairment in an amyloid precursor protein/presenilin 1 transgenic mouse model of Alzheimer's disease

Authors:
- Qing Zhu
- Nianping Zhang
- Nan Hu
- Rongrong Jiang
- Huicong Lu
- Aiguo Xuan
- Dahong Long
- Yan Chen
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Affiliations: Department of Rehabilitation Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, P.R. China, The Teaching and Research Section of Surgery, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China, Department of Human Anatomy, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China
Published online on: January 8, 2020 https://doi.org/10.3892/mmr.2020.10918
Pages: 1172-1180
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Alzheimer's disease (AD) is the most prevalent age‑related neurodegenerative disorder. It is featured by the progressive accumulation of β‑amyloid (Aβ) plaques and neurofibrillary tangles. This can eventually lead to a decrease of cholinergic neurons in the basal forebrain. Stem cell transplantation is an effective treatment for neurodegenerative diseases. Previous studies have revealed that different types of stem or progenitor cells can mitigate cognition impairment in different Alzheimer's disease mouse models. However, understanding the underlying mechanisms of neural stem cell (NSC) therapies for AD requires further investigation. In the present study, the effects and the underlying mechanisms of the treatment of AD by NSCs are reported. The latter were labelled with the enhanced green fluorescent protein (EGFP) prior to implantation into the bilateral hippocampus of an amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic (Tg) mouse model of AD. It was observed that the number of basal forebrain cholinergic neurons was restored and the expression of choline acetyltransferase (ChAT) protein was increased. Moreover, the levels of synaptophysin (SYP), postsynaptic density protein 95 (PSD‑95) and microtubule‑associated protein (MAP‑2) were significantly increased in the hippocampus of NSC‑treated AD mice. Notably, spatial learning and memory were both improved after transplantation of NSCs. In conclusion, the present study revealed that NSC transplantation improved learning and memory functions in an AD mouse model. This treatment allowed repairing of basal forebrain cholinergic neurons and increased the expression of the cognition‑related proteins SYP, PSD‑95 and MAP‑2 in the hippocampus.

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