Yamasaki Tritia R, Blurton-Jones Mathew, Morrissette Debbi A, Kitazawa Masashi, Oddo Salvatore, LaFerla Frank M
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, USA.
J Neurosci. 2007 Oct 31;27(44):11925-33. doi: 10.1523/JNEUROSCI.1627-07.2007.
Neuronal loss is a major pathological outcome of many common neurological disorders, including ischemia, traumatic brain injury, and Alzheimer disease. Stem cell-based approaches have received considerable attention as a potential means of treatment, although it remains to be determined whether stem cells can ameliorate memory dysfunction, a devastating component of these disorders. We generated a transgenic mouse model in which the tetracycline-off system is used to regulate expression of diphtheria toxin A chain. After induction, we find progressive neuronal loss primarily within the hippocampus, leading to specific impairments in memory. We find that neural stem cells transplanted into the brain after neuronal ablation survive, migrate, differentiate and, most significantly, improve memory. These results show that stem cells may have therapeutic value in diseases and conditions that result in memory loss.
神经元丢失是许多常见神经疾病的主要病理结果，包括缺血性疾病、创伤性脑损伤和阿尔茨海默病。基于干细胞的治疗方法作为一种潜在的治疗手段受到了广泛关注，尽管干细胞是否能够改善记忆功能障碍（这些疾病的一个毁灭性组成部分）仍有待确定。我们构建了一种转基因小鼠模型，其中使用四环素调控系统来调节白喉毒素A链的表达。诱导后，我们发现主要在海马体内出现进行性神经元丢失，导致记忆出现特定损伤。我们发现，在神经元消融后移植到脑内的神经干细胞能够存活、迁移、分化，并且最显著的是能够改善记忆。这些结果表明，干细胞可能对导致记忆丧失的疾病和病症具有治疗价值。
