Altered inhibitory function in hippocampal CA2 contributes in social memory deficits in Alzheimer's mouse model.
Altered inhibitory function in hippocampal CA2 contributes in social memory deficits in Alzheimer's mouse model.
复制标题
DOI：
10.1016/j.isci.2022.103895
复制
发表时间：
2022-03-18
期刊：
影响因子：
5.8
通讯作者：
Verret L
中科院分区：
文献类型：
--
作者：
Rey CC;Robert V;Bouisset G;Loisy M;Lopez S;Cattaud V;Lejards C;Piskorowski RA;Rampon C;Chevaleyre V;Verret L
表达小白蛋白（PV）的中间神经元通常与特定的细胞外基质神经元周网（PNN）相关，在阿尔茨海默病（AD）的脑活动和记忆性能的改变中起关键作用。这些神经元的完整性对于海马子区CA 2的正常功能以及社会记忆的形成至关重要。在这里，我们发现AD小鼠模型的社交记忆缺陷与PV细胞周围PNN的存在减少和CA 2区的长期突触可塑性有关。此外，单次局部注射生长因子神经调节蛋白-1（NRG 1）足以恢复这些小鼠的PV/PNN水平和社会记忆表现。因此，在CA 2区的PV/PNN中断可能在AD小鼠的社会记忆缺陷中发挥因果作用，并且激活PV细胞促成熟通路可能足以恢复社会记忆。Tg 2576小鼠AD模型具有正常的社交能力，但不能形成社交记忆Tg 2576小鼠海马区CA 2中可检测到的PV中间神经元和PNN较少Tg 2576小鼠CA 2中PV依赖的长期可塑性改变CA 2中的NRG 1增加PV/PNN并恢复这些AD小鼠的社交记忆行为神经科学;分子神经科学;细胞神经科学
Parvalbumin (PV)-expressing interneurons which are often associated with the specific extracellular matrix perineuronal net (PNN) play a critical role in the alteration of brain activity and memory performance in Alzheimer’s disease (AD). The integrity of these neurons is crucial for normal functioning of the hippocampal subfield CA2, and hence, social memory formation. Here, we find that social memory deficits of mouse models of AD are associated with decreased presence of PNN around PV cells and long-term synaptic plasticity in area CA2. Furthermore, single local injection of the growth factor neuregulin-1 (NRG1) is sufficient to restore both PV/PNN levels and social memory performance of these mice. Thus, the PV/PNN disruption in area CA2 could play a causal role in social memory deficits of AD mice, and activating PV cell pro-maturation pathways may be sufficient to restore social memory. Tg2576 mouse model of AD have normal sociability, but cannot form social memory Tg2576 mice have less detectable PV interneurons and PNN in hippocampal area CA2 PV-dependent long-term plasticity is altered in CA2 of Tg2576 mice NRG1 in CA2 increases PV/PNN and restores social memory of these AD mice Behavioral neuroscience; Molecular neuroscience; Cellular neuroscience
登录
查看更多内容
影响因子：
16.2
作者：
Chevaleyre V;Siegelbaum SA
通讯作者：
Siegelbaum SA
影响因子：
2.9
作者：
Botcher NA;Falck JE;Thomson AM;Mercer A
通讯作者：
Mercer A
影响因子：
4.2
作者：
Cattaud, Vanessa;Bezzina, Charlotte;Verret, Laure
通讯作者：
Verret, Laure
影响因子：
8.8
作者：
Dominguez, Soledad;Rey, Christophe Clement;Chevaleyre, Vivien
通讯作者：
Chevaleyre, Vivien
影响因子：
5.3
作者：
Gu, Yu;Trinh Tran;Quinlan, Elizabeth M.
通讯作者：
Quinlan, Elizabeth M.