PMID- 35781287 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2058-7716 (Print) IS - 2058-7716 (Electronic) IS - 2058-7716 (Linking) VI - 8 IP - 1 DP - 2022 Jul 4 TI - MicroRNA-206 down-regulated human umbilical cord mesenchymal stem cells alleviate cognitive decline in D-galactose-induced aging mice. PG - 304 LID - 10.1038/s41420-022-01097-z [doi] LID - 304 AB - BACKGROUND: Non-pathological cognitive decline is a neurodegenerative condition associated with brain aging owing to epigenetic changes, telomere shortening, stem cells exhaustion, or altered differentiation. Human umbilical cord mesenchymal stem cells (hUCMSCs) have shown excellent therapeutic prospects on the hallmarks of aging. In this study, we aimed to elucidate the role of hUCMSCs with down-regulated miRNA-206 (hUCMSCs anti-miR-206) on cognitive decline and the underlying mechanism. METHODS: After daily subcutaneous injection of D-gal (500 mg/kg/d) for 8 weeks, 17-week-old male C57BL/6 J mice were stem cells transplanted by lateral ventricular localization injection. During the 10-day rest period, were tested the behavioral experiments applied to cognitive behavior in the hippocampus. And then, the mice were sacrificed for sampling to complete the molecular and morphological experiments. RESULTS: Our behavioral experiments of open field test (OFT), new object recognition test (NOR), and Y-maze revealed that D-galactose (D-gal)-induced aging mice treated with hUCMSCs anti-miR-206 had no obvious spontaneous activity disorder and had recovery in learning and spatial memory ability compared with the PBS-treated group. The hUCMSCs anti-miR-206 reconstituted neuronal physiological function in the hippocampal regions of the aging mice with an increase of Nissl bodies and the overexpression of Egr-1, BDNF, and PSD-95. CONCLUSION: This study first reports that hUCMSCs anti-miR-206 could provide a novel stem cell-based antiaging therapeutic approach. CI - (c) 2022. The Author(s). FAU - Zhang, Yuying AU - Zhang Y AD - Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China. FAU - Deng, Weiyue AU - Deng W AD - Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China. FAU - Wang, Wei AU - Wang W AD - Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China. FAU - Song, Aishi AU - Song A AD - Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China. FAU - Mukama, Omar AU - Mukama O AD - CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. FAU - Deng, Sihao AU - Deng S AD - Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China. FAU - Han, Xiaobo AU - Han X AD - CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. FAU - De Dieu Habimana, Jean AU - De Dieu Habimana J AD - CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. FAU - Peng, Kexin AU - Peng K AD - NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China. FAU - Ni, Bin AU - Ni B AD - NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China. FAU - Zhang, Shusheng AU - Zhang S AD - Changsha Stomatological Hospital, Changsha, China. FAU - Huang, Jufang AU - Huang J AD - Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China. FAU - Yan, Xiao-Xin AU - Yan XX AD - Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China. FAU - Li, Zhiyuan AU - Li Z AUID- ORCID: 0000-0001-5963-4225 AD - Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China. li_zhiyuan@gibh.ac.cn. AD - CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. li_zhiyuan@gibh.ac.cn. AD - NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China. li_zhiyuan@gibh.ac.cn. AD - Changsha Stomatological Hospital, Changsha, China. li_zhiyuan@gibh.ac.cn. AD - Bioland Laboratory, Guangzhou, China. li_zhiyuan@gibh.ac.cn. AD - GZMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China. li_zhiyuan@gibh.ac.cn. AD - GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou, China. li_zhiyuan@gibh.ac.cn. LA - eng PT - Journal Article DEP - 20220704 PL - United States TA - Cell Death Discov JT - Cell death discovery JID - 101665035 PMC - PMC9250929 COIS- The authors declare no competing interests. EDAT- 2022/07/06 06:00 MHDA- 2022/07/06 06:01 PMCR- 2022/07/04 CRDT- 2022/07/05 08:58 PHST- 2022/02/14 00:00 [received] PHST- 2022/06/21 00:00 [accepted] PHST- 2022/05/09 00:00 [revised] PHST- 2022/07/05 08:58 [entrez] PHST- 2022/07/06 06:00 [pubmed] PHST- 2022/07/06 06:01 [medline] PHST- 2022/07/04 00:00 [pmc-release] AID - 10.1038/s41420-022-01097-z [pii] AID - 1097 [pii] AID - 10.1038/s41420-022-01097-z [doi] PST - epublish SO - Cell Death Discov. 2022 Jul 4;8(1):304. doi: 10.1038/s41420-022-01097-z.