Dentate gyrus mediates cognitive function in the Ts65Dn/DnJ mouse model of Down syndrome.
Dentate gyrus mediates cognitive function in the Ts65Dn/DnJ mouse model of Down syndrome.
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DOI：
10.1002/hipo.22229
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发表时间：
2014-03
期刊：
影响因子：
3.5
通讯作者：
Korenberg, Julie R.
中科院分区：
文献类型：
--
作者：
Smith, Genevieve K.;Kesner, Raymond P.;Korenberg, Julie R.
在唐氏综合征（DS）的Ts 65 Dn/DnJ小鼠模型中，海马学习和记忆缺陷是支持该小鼠作为DS的有效认知模型的最稳健的特征。虽然过度的GABA能抑制提示齿状回（DG）功能障碍，但其在DS中扰乱DG功能的作用尚不清楚。我们假设，在Ts 65 Dn/DnJ小鼠，DG的具体作用是在其支持的上下文和空间信息的干扰。支持这一假设来自大鼠DG病变，表现出类似的赤字。为了验证这一假设，我们开发了一系列新的自发探索任务，强调认识空间和上下文线索的重要性，并涉及DG功能。该探索性组合的结果表明，Ts 65 Dn/DnJ小鼠在DG依赖性短期识别测试中受损，该测试涉及具有上下文线索的物体识别、原地识别和相对于野生型同窝对照的度量距离识别。此外，虽然Ts 65 Dn/DnJ小鼠可以识别对象的新奇性，在没有上下文线索后5分钟的延迟，他们不能这样做后，延迟24小时，这表明与CA 1介导的巩固的问题。结果还表明，Ts 65 Dn/DnJ小鼠在由嗅周皮层（PRh）介导的任务（物体识别和脑物体识别）中没有受损。这些结果暗示DG作为一个特定的治疗靶点和PRh作为一个潜在的治疗力量，为未来的研究，以改善学习和记忆的DS。
In the Ts65Dn/DnJ mouse model of Down syndrome (DS), hippocampal deficits of learning and memory are the most robust features supporting this mouse as a valid cognitive model of DS. Although dentate gyrus (DG) dysfunction is suggested by excessive GABAergic inhibition, its role in perturbing DG functions in DS is unknown. We hypothesize that in the Ts65Dn/DnJ mouse, the specific role of the DG is disturbed in its support of contextual and spatial information. Support for this hypothesis comes from rats with DG lesions that show similar deficits. In order to test this hypothesis, we have developed a novel series of spontaneous exploratory tasks that emphasize the importance of recognizing spatial and contextual cues and that involve DG function. The results with this exploratory battery show that Ts65Dn/DnJ mice are impaired in DG-dependent short-term recognition tests involving object recognition with contextual cues, in place recognition and in metric distance recognition relative to wild type littermate controls. Further, whereas Ts65Dn/DnJ mice can recognize object novelty in the absence of contextual cues after a 5-min delay, they cannot do so after a delay of 24 h, suggesting a problem with CA1-mediated consolidation. The results also show that Ts65Dn/DnJ mice are not impaired in tasks (object recognition and configural object recognition) that are mediated by the perirhinal cortex (PRh). These results implicate the DG as a specific therapeutic target and the PRh as a potential therapeutic strength for future research to ameliorate learning and memory in DS.
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影响因子：
2.5
作者：
Belichenko, PV;Masliah, E;Mobley, WC
通讯作者：
Mobley, WC
DOI：
10.1177/0269881111405366
发表时间：
2011-08
期刊：
Journal of psychopharmacology (Oxford, England)
影响因子：
--
作者：
Braudeau J;Delatour B;Duchon A;Pereira PL;Dauphinot L;de Chaumont F;Olivo-Marin JC;Dodd RH;Hérault Y;Potier MC
通讯作者：
Potier MC
影响因子：
2.5
作者：
Popov, Victor I.;Kleschevnikov, Alexander M.;Belichenko, Pavel V.
通讯作者：
Belichenko, Pavel V.
影响因子：
2.6
作者：
Seregaza, Zohra;Roubertoux, Pierre L.;Soumireu-Mourat, Bernard
通讯作者：
Soumireu-Mourat, Bernard
影响因子：
2.7
作者：
Dix, SL;Aggleton, JP
通讯作者：
Aggleton, JP