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挽救过度激活的小胶质细胞可恢复唐氏综合征 DP(16) 小鼠模型幼小动物的认知功能。

Rescuing Over-activated Microglia Restores Cognitive Performance in Juvenile Animals of the Dp(16) Mouse Model of Down Syndrome.

机构信息

BIO@SNS, Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126 Pisa, Italy; Brain Development and Disease Laboratory, Istituto Italiano di Tecnologia, via Morego 30, 16163 Genova, Italy.

Brain Development and Disease Laboratory, Istituto Italiano di Tecnologia, via Morego 30, 16163 Genova, Italy.

出版信息

Neuron. 2020 Dec 9;108(5):887-904.e12. doi: 10.1016/j.neuron.2020.09.010. Epub 2020 Oct 6.

DOI:10.1016/j.neuron.2020.09.010
PMID:33027640
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7736620/
Abstract

Microglia are brain-resident immune cells and regulate mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual disability, is caused by a supernumerary chromosome 21, containing also genes related to the immune system. In the hippocampus of the Dp(16) mouse model of DS and DS individuals, we found activated microglia, as assessed by their morphology; activation markers; and, for DS mice, electrophysiological profile. Accordingly, we found increased pro-inflammatory cytokine levels and altered interferon signaling in Dp(16) hippocampi. DS mice also showed decreased spine density and activity of hippocampal neurons and hippocampus-dependent cognitive behavioral deficits. Depletion of defective microglia or treatment with a commonly used anti-inflammatory drug rescued the neuronal spine and activity impairments and cognitive deficits in juvenile Dp(16) mice. Our results suggest an involvement of microglia in Dp(16)-mouse cognitive deficits and identify a new potential therapeutic approach for cognitive disabilities in DS individuals.

摘要

小胶质细胞是大脑中固有的免疫细胞，调节认知功能所必需的机制。唐氏综合征（DS）是最常见的遗传性智力障碍病因，由额外的 21 号染色体引起，其中还包含与免疫系统相关的基因。在 DS 患者和 Dp(16) 小鼠模型的海马体中，我们发现小胶质细胞被激活，其形态、激活标志物以及 Dp(16) 小鼠的电生理特征均可以证明这一点。相应地，我们发现 Dp(16) 海马体中的促炎细胞因子水平升高和干扰素信号通路改变。DS 小鼠还表现出海马神经元棘突密度降低和活性降低，以及海马体依赖的认知行为缺陷。耗尽有缺陷的小胶质细胞或用常用的抗炎药物治疗可挽救幼年 Dp(16) 小鼠的神经元棘突和活性损伤以及认知缺陷。我们的研究结果表明小胶质细胞参与 Dp(16) 小鼠的认知缺陷，并为 DS 患者的认知障碍提供了一种新的潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19af/7736620/4d564b9c4709/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19af/7736620/46bdcda7c7b1/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19af/7736620/8dfacc649d86/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19af/7736620/4d564b9c4709/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19af/7736620/46bdcda7c7b1/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19af/7736620/8dfacc649d86/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19af/7736620/4d564b9c4709/gr3.jpg

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