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治疗产后早期的回路缺陷可延缓小鼠亨廷顿氏病的发病和病理
作者:小柯机器人 发布时间:2022/9/25 20:55:48

法国格勒诺布尔大学Sandrine Humbert研究小组发现,治疗产后早期的回路缺陷可延缓小鼠亨廷顿氏病的发病和病理。这一研究成果发表在2022年9月23日出版的国际学术期刊《科学》上。

据研究人员介绍,最近的证据表明,即使是与晚期亨廷顿病(HD)相关的亨廷顿基因的轻微突变,也会破坏人类神经发育的各个方面。

为了确定这些看似微妙的早期缺陷是否影响成年神经功能,研究人员调查了新生HD小鼠的神经回路生理学。在出生后的第一周,HD小鼠的皮质2/3层兴奋性突触活动比野生型小鼠少,表达的谷氨酸受体较少,并显示出感觉运动障碍。该回路在出生后第二周会自我正常化,但小鼠仍然会发展成HD。然而,在新生儿期通过药物加强谷氨酸传递,可以挽救这些缺陷,并保留感觉运动功能、认知、脊柱和突触密度以及HD成年小鼠的脑区体积。

附:英文原文

Title: Treating early postnatal circuit defect delays Huntington’s disease onset and pathology in mice

Author: Barbara Yael Braz, Doris Wennagel, Leslie Ratié, Diego Alves Rodrigues de Souza, Jean Christophe Deloulme, Emmanuel L. Barbier, Alain Buisson, Fabien Lanté, Sandrine Humbert

Issue&Volume: 2022-09-23

Abstract: Recent evidence has shown that even mild mutations in the Huntingtin gene that are associated with late-onset Huntington’s disease (HD) disrupt various aspects of human neurodevelopment. To determine whether these seemingly subtle early defects affect adult neural function, we investigated neural circuit physiology in newborn HD mice. During the first postnatal week, HD mice have less cortical layer 2/3 excitatory synaptic activity than wild-type mice, express fewer glutamatergic receptors, and show sensorimotor deficits. The circuit self-normalizes in the second postnatal week but the mice nonetheless develop HD. Pharmacologically enhancing glutamatergic transmission during the neonatal period, however, rescues these deficits and preserves sensorimotor function, cognition, and spine and synapse density as well as brain region volume in HD adult mice.

DOI: abq5011

Source: https://www.science.org/doi/10.1126/science.abq5011

 

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037