GIT1 regulates synaptic structural plasticity underlying learning.
GIT1 regulates synaptic structural plasticity underlying learning.
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DOI：
10.1371/journal.pone.0194350
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Premont RT
中科院分区：
文献类型：
--
作者：
Martyn AC;Toth K;Schmalzigaug R;Hedrick NG;Rodriguiz RM;Yasuda R;Wetsel WC;Premont RT
信号支架蛋白GIT 1在整个大脑中广泛表达，但其在体内的功能仍然难以捉摸。缺乏GIT1的小鼠被认为是注意力缺陷多动障碍的模型，这是由于基础运动活动的改变以及精神兴奋剂安非他明对矛盾运动的抑制。由于我们之前已经证明GIT1敲除小鼠具有正常的运动活动，因此我们在这里更详细地检查了GIT1缺陷小鼠的ADHD样行为，并且既没有发现多动症也没有发现安非他明诱导的运动抑制。相反，GIT1缺陷小鼠表现出严重的学习和记忆缺陷，突触结构可塑性降低，与智力残疾表型一致。我们的结论是，GIT1单独的损失是不足以驱动一个强大的ADHD表型在不同品系的小鼠。相比之下，在这里和其他使用不同GIT 1敲除系的研究中观察到了多种学习和记忆缺陷，这与突触结构可塑性改变相关的主要智力残疾表型一致。
The signaling scaffold protein GIT1 is expressed widely throughout the brain, but its function in vivo remains elusive. Mice lacking GIT1 have been proposed as a model for attention deficit-hyperactivity disorder, due to alterations in basal locomotor activity as well as paradoxical locomotor suppression by the psychostimulant amphetamine. Since we had previously shown that GIT1-knockout mice have normal locomotor activity, here we examined GIT1-deficient mice for ADHD-like behavior in more detail, and find neither hyperactivity nor amphetamine-induced locomotor suppression. Instead, GIT1-deficient mice exhibit profound learning and memory defects and reduced synaptic structural plasticity, consistent with an intellectual disability phenotype. We conclude that loss of GIT1 alone is insufficient to drive a robust ADHD phenotype in distinct strains of mice. In contrast, multiple learning and memory defects have been observed here and in other studies using distinct GIT1-knockout lines, consistent with a predominant intellectual disability phenotype related to altered synaptic structural plasticity.
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DOI：
10.1111/j.1601-183x.2009.00555.x
发表时间：
2010-04
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
Porton B;Rodriguiz RM;Phillips LE;Gilbert JW 4th;Feng J;Greengard P;Kao HT;Wetsel WC
通讯作者：
Wetsel WC
影响因子：
64.8
作者：
Hedrick NG;Harward SC;Hall CE;Murakoshi H;McNamara JO;Yasuda R
通讯作者：
Yasuda R
影响因子：
8.8
作者：
Podufall, Jasmin;Tian, Rui;Haucke, Volker
通讯作者：
Haucke, Volker
影响因子：
64.8
作者：
Harward SC;Hedrick NG;Hall CE;Parra-Bueno P;Milner TA;Pan E;Laviv T;Hempstead BL;Yasuda R;McNamara JO
通讯作者：
McNamara JO
影响因子：
15.9
作者：
Murakoshi H;Yasuda R
通讯作者：
Yasuda R