Motivational disturbances and effects of L-dopa administration in neurofibromatosis-1 model mice.
Motivational disturbances and effects of L-dopa administration in neurofibromatosis-1 model mice.
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DOI：
10.1371/journal.pone.0066024
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gutmann DH
中科院分区：
文献类型：
--
作者：
Wozniak DF;Diggs-Andrews KA;Conyers S;Yuede CM;Dearborn JT;Brown JA;Tokuda K;Izumi Y;Zorumski CF;Gutmann DH
患有1型神经纤维瘤病(NF1)的儿童经常有认知和行为障碍。其中一些缺陷已经在患视神经胶质瘤的NF1基因工程小鼠(NF1 OPG小鼠)中成功地建立了模型。在目前的研究中，我们表明异常的动机影响会影响Nf1 OPG小鼠的行为，特别是在它们对新的环境刺激的反应方面。例如，与WT对照组相比，Nf1 OPG小鼠在Y形迷宫中自发改变的次数更少，手臂进入的次数也更少。然而，对标准化交替数据的分析表明，这些差异并不是由于空间工作记忆缺陷造成的。其他已报道的行为结果(例如，下面的开场测试)表明，与运动活动/自发运动的简单差异相比，对新奇事物和/或其他动机影响的不同反应可能是这些类型行为的更重要的决定因素。重要的是，在Nf1 OPG小鼠的海马片中观察到了正常的长期抑郁。高架加迷宫测试的结果表明，Nf1 OPG和WT对照组小鼠之间的探索活动差异可能取决于测量探索的环境背景(例如，威胁或非威胁)。尽管给予L-多巴(50 mg/kg)可纠正这种异常的嗅觉偏好行为，但NF1 OPG小鼠在一种新的孔板上的探索性穿孔也减少了，并表现出异常的嗅觉偏好。NF1 OPG小鼠对一种新的开阔场表现出减弱的反应，表现为行走活动和站立能力的下降，但仅在会话的前10分钟内。重要的是，NF1 OPG小鼠对悬挂在场地一侧的一个新的悬挂物表现出调查饲养缺陷，而L-多巴政府并没有营救它。总而言之，我们的结果为评估旨在改善NF1相关认知/行为缺陷的治疗方法提供了重要的新数据。
Children with neurofibromatosis type 1 (NF1) frequently have cognitive and behavioral deficits. Some of these deficits have been successfully modeled in Nf1 genetically-engineered mice that develop optic gliomas (Nf1 OPG mice). In the current study, we show that abnormal motivational influences affect the behavior of Nf1 OPG mice, particularly with regard to their response to novel environmental stimuli. For example, Nf1 OPG mice made fewer spontaneous alternations in a Y-maze and fewer arm entries relative to WT controls. However, analysis of normalized alternation data demonstrated that these differences were not due to a spatial working memory deficit. Other reported behavioral results (e.g., open-field test, below) suggest that differential responses to novelty and/or other motivational influences may be more important determinants of these kinds of behavior than simple differences in locomotor activity/spontaneous movements. Importantly, normal long-term depression was observed in hippocampal slices from Nf1 OPG mice. Results from elevated plus maze testing showed that differences in exploratory activity between Nf1 OPG and WT control mice may be dependent on the environmental context (e.g., threatening or non-threatening) under which exploration is being measured. Nf1 OPG mice also exhibited decreased exploratory hole poking in a novel holeboard and showed abnormal olfactory preferences, although L-dopa (50 mg/kg) administration resolved the abnormal olfactory preference behaviors. Nf1 OPG mice displayed an attenuated response to a novel open field in terms of decreased ambulatory activity and rearing but only during the first 10 min of the session. Importantly, Nf1 OPG mice demonstrated investigative rearing deficits with regard to a novel hanging object suspended on one side of the field which were not rescued by L-dopa administration. Collectively, our results provide new data important for evaluating therapeutic treatments aimed at ameliorating NF1-associated cognitive/behavioral deficits.
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ERK信号传导的神经纤维素调节调节GABA释放和学习。
影响因子：
64.5
作者：
Cui Y;Costa RM;Murphy GG;Elgersma Y;Zhu Y;Gutmann DH;Parada LF;Mody I;Silva AJ
通讯作者：
Silva AJ
影响因子：
16.2
作者：
Etkin, A;Alarcón, JM;Kandel, ER
通讯作者：
Kandel, ER
影响因子：
3.5
作者：
Brown, Jacquelyn A.;Emnett, Ryan J.;Gutmann, David H.
通讯作者：
Gutmann, David H.
影响因子：
5.3
作者：
Brown, Jacquelyn A.;Xu, Jinbin;Gutmann, David H.
通讯作者：
Gutmann, David H.
DOI：
10.1523/jneurosci.4762-12.2013
发表时间：
2013-02-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dougherty JD;Maloney SE;Wozniak DF;Rieger MA;Sonnenblick L;Coppola G;Mahieu NG;Zhang J;Cai J;Patti GJ;Abrahams BS;Geschwind DH;Heintz N
通讯作者：
Heintz N