Selective inhibition of somatostatin-positive dentate hilar interneurons induces age-related cellular changes and cognitive dysfunction.
Selective inhibition of somatostatin-positive dentate hilar interneurons induces age-related cellular changes and cognitive dysfunction.
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DOI：
10.1093/pnasnexus/pgad134
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发表时间：
2023-05
期刊：
影响因子：
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通讯作者：
Rudolph, Uwe
中科院分区：
文献类型：
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作者：
Lyu, Jinrui;Nagarajan, Rajasekar;Kambali, Maltesh;Wang, Muxiao;Rudolph, Uwe
与年龄相关的海马功能损伤的细胞基础尚不完全清楚。为了评估齿状回（DG）门中生长抑素阳性（Sst+）中间神经元在此过程中的作用，我们通过化学遗传学方法抑制了DG门中的Sst+中间神经元。这些神经元的慢性化学遗传学抑制（CCI）导致 DG 门中 c-Fos 染色增加，DG 中表达 GAD67 和 Sst 的中间神经元百分比减少，以及 DG、CA3 和 CA1 中小胶质细胞活化增加。 DG 和 CA1 中的总树突长度和树突棘密度减少，表明树突复杂性降低。在行为上，物体识别任务中的识别指数和Y迷宫中自发交替的百分比下降，而在莫里斯水迷宫的初始学习和逆转学习中，找到隐藏平台的潜伏期增加，表明认知功能障碍。我们的研究结果确定了 DG 门中 Sst+ 中间神经元功能降低与认知能力下降的因果关系，并表明这种功能降低可能导致与年龄相关的学习和记忆障碍。此外，我们的 CCI 小鼠可能代表了海马衰老的细胞定义模型。
The cellular basis of age-related impairments of hippocampal function is not fully understood. In order to evaluate the role of somatostatin-positive (Sst+) interneurons in the dentate gyrus (DG) hilus in this process, we chemogenetically inhibited Sst+ interneurons in the DG hilus. Chronic chemogenetic inhibition (CCI) of these neurons resulted in increased c-Fos staining in the DG hilus, a decrease in the percentage of GAD67- and of Sst-expressing interneurons in the DG, and increased microglial activation in DG, CA3, and CA1. Total dendritic length and spine density were reduced in DG and CA1, suggesting reduced dendritic complexity. Behaviorally, the recognition index in an object recognition task and the percentage of spontaneous alternations in the Y-maze were decreased, while in both initial and reversal learning in the Morris water maze, the latencies to find the hidden platform were increased, suggesting cognitive dysfunction. Our findings establish a causal role for a reduced function of Sst+ interneurons in the DG hilus for cognitive decline and suggest that this reduced function may contribute to age-related impairments of learning and memory. Furthermore, our CCI mice may represent a cellularly defined model of hippocampal aging.
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DOI：
10.1073/pnas.051614698
发表时间：
2001-03-13
影响因子：
11.1
作者：
Liu, WS;Pesold, C;Costa, E
通讯作者：
Costa, E
影响因子：
16.2
作者：
Bakker A;Krauss GL;Albert MS;Speck CL;Jones LR;Stark CE;Yassa MA;Bassett SS;Shelton AL;Gallagher M
通讯作者：
Gallagher M
影响因子：
4.6
作者：
Jendryka, Martin;Palchaudhuri, Monika;Pekcec, Anton
通讯作者：
Pekcec, Anton
影响因子：
3.4
作者：
Kersten, Maxi;Rabbe, Theresa;Kirschstein, Timo
通讯作者：
Kirschstein, Timo
DOI：
10.1038/npp.2009.207
发表时间：
2010-03
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
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作者：
通讯作者：
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