利用反义寡核苷酸抑制PTB可产生治疗性新生神经

作者：王韵壹、李英、熊慧卿

本期文章：《自然—神经科学》：Online/在线发表

美国加州大学Don W. Cleveland研究团队近日取得一项新成果。经过不懈努力，他们发现利用反义寡核苷酸抑制PTB可产生治疗性新生神经元。相关论文于2021年6月3日发表于国际学术期刊《自然-神经科学》杂志。

研究人员通过单次注射到脑脊液中的反义寡核苷酸瞬时抑制聚嘧啶束结合蛋白，成功地在老年小鼠的大脑皮层和齿状回中诱导了新生神经元。径向神经胶质样细胞和其他表达 GFAP 的细胞转化为新的神经元，并在模拟正常神经元成熟的2 个月时间内获得了成熟神经元的特征。新神经元在功能上整合到内源性回路中并改变小鼠的行为。因此，可以通过治疗上可行的方法在衰老大脑的齿状回中产生新的神经元，从而为产生新生神经元来替代因神经退行性疾病而丢失的神经元开辟了前景。

据悉，通过将神经胶质细胞重编程为神经元来增强成体神经发生的方法能够在成体神经系统中产生新的神经元。现在急需在治疗上可行的方法来诱导新生神经元，以将这一理念引入临床应用。

附：英文原文

Title: Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB

Author: Roy Maimon, Carlos Chillon-Marinas, Cedric E. Snethlage, Sarthak M. Singhal, Melissa McAlonis-Downes, Karen Ling, Frank Rigo, C. Frank Bennett, Sandrine Da Cruz, Thomas S. Hnasko, Alysson R. Muotri, Don W. Cleveland

Issue&Volume: 2021-06-03

Abstract: Methods to enhance adult neurogenesis by reprogramming glial cells into neurons enable production of new neurons in the adult nervous system. Development of therapeutically viable approaches to induce new neurons is now required to bring this concept to clinical application. Here, we successfully generate new neurons in the cortex and dentate gyrus of the aged adult mouse brain by transiently suppressing polypyrimidine tract binding protein 1 using an antisense oligonucleotide delivered by a single injection into cerebral spinal fluid. Radial glial-like cells and other GFAP-expressing cells convert into new neurons that, over a 2-month period, acquire mature neuronal character in a process mimicking normal neuronal maturation. The new neurons functionally integrate into endogenous circuits and modify mouse behavior. Thus, generation of new neurons in the dentate gyrus of the aging brain can be achieved with a therapeutically feasible approach, thereby opening prospects for production of neurons to replace those lost to neurodegenerative disease. Maimon et al. demonstrate a therapeutically viable approach, single-dose injection of a DNA drug to suppress synthesis of PTB, to generate new neurons in the aged mouse hippocampus and enhance memory after their integration into endogenous circuits.

DOI: 10.1038/s41593-021-00864-y

Source: https://www.nature.com/articles/s41593-021-00864-y

期刊信息

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：21.126
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex