Cholinesterase Inhibitor Reveals Synergistic Potential for Neural Stem Cell-Based Therapy in the 5xFAD Mouse Model of Alzheimer's Disease

胆碱酯酶抑制剂在阿尔茨海默病 5xFAD 小鼠模型中显示出神经干细胞治疗的协同潜力

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作者:Cheng-Chun Wu #, Yung-Kuo Lee #, Jui-Kang Tsai, Yu-Ting Su, Yu-Cheng Ho, Tian-Huei Chu, Kuang-Ti Chen, Chen-Lin Chang, Jui-Shen Chen

Conclusion

Combining ChEIs with NSC transplantation produces synergistic effects in AD treatment. This approach highlights the potential of integrating these therapies to develop more effective strategies for managing Alzheimer's disease.

Methods

Neural stem cells (NSCs) were injected into the hippocampus of the 5xFAD AD mice using a stereotactic technique. Following this, donepezil or a placebo was administered for one month. We assessed behavioral improvements, survival and health of the grafts, and changes in synaptic density.

Results

The AD mice demonstrated cognitive impairment in both the Morris water maze and novel object recognition tests. In groups receiving stem cell therapy, donepezil enhanced the survival and neuronal differentiation of grafted NSCs, promoting the establishment of synaptic connections with the host brain. The combined treatment with donepezil and NSC transplantation more effectively increased synaptic density and improved behavioral performance in AD mice compared to NSC transplantation alone.

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