Takeuchi Yukiko, Okinaka Yuka, Ogawa Yuko, Kikuchi-Taura Akie, Kataoka Yosky, Gul Sheraz, Claussen Carsten, Boltze Johannes, Taguchi Akihiko
Department of Regenerative Medicine Research, Foundation for Biomedical Research and Innovation at Kobe, Hyogo, Japan.
Multi-Modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, RIKEN, Hyogo, Japan.
Front Aging Neurosci. 2020 Jun 11;12:170. doi: 10.3389/fnagi.2020.00170. eCollection 2020.
We recently reported that intravenous bone marrow mononuclear cell (BM-MNC) transplantation in stroke improves neurological function through improvement of cerebral metabolism. Cerebral metabolism is known to diminish with aging, and the reduction of metabolism is one of the presumed causes of neurological decline in the elderly. We report herein that transcription of glucose transporters, monocarboxylate transporters, and Na/K-ATPase is downregulated in the hippocampus of aged mice with impaired neurological functions. Intravenous BM-MNC transplantation in aged mice stimulated the transcription of glucose transporter 1 and Na/K-ATPase α1 followed by restoration of neurological function. As glucose transporters and Na/K-ATPases are closely related to cerebral metabolism and neurological function, our data indicate that BM-MNC transplantation in aged mice has the potential to restore neurological function by activating transcription of glucose transporter and Na/K-ATPase. Furthermore, our data indicate that changes in transcription of glucose transporter and Na/K-ATPase could be surrogate biomarkers for age-related neurological impairment as well as quantifying the efficacy of therapies.
我们最近报道,中风患者静脉注射骨髓单个核细胞(BM-MNC)可通过改善脑代谢来改善神经功能。已知脑代谢会随着衰老而减弱,而代谢降低是老年人神经功能衰退的推测原因之一。我们在此报告,在神经功能受损的老年小鼠海马体中,葡萄糖转运蛋白、单羧酸转运蛋白和钠钾ATP酶的转录下调。对老年小鼠进行静脉BM-MNC移植可刺激葡萄糖转运蛋白1和钠钾ATP酶α1的转录,随后神经功能得以恢复。由于葡萄糖转运蛋白和钠钾ATP酶与脑代谢和神经功能密切相关,我们的数据表明,对老年小鼠进行BM-MNC移植有可能通过激活葡萄糖转运蛋白和钠钾ATP酶的转录来恢复神经功能。此外,我们的数据表明,葡萄糖转运蛋白和钠钾ATP酶转录的变化可能是与年龄相关的神经损伤的替代生物标志物,也可用于量化治疗效果。