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CRMP2 improves memory deficits by enhancing the maturation of neuronal dendritic spines after traumatic brain injury.
Experimental Neurology ( IF 5.3 ) Pub Date : 2020-02-19 , DOI: 10.1016/j.expneurol.2020.113253
Yi-Yu Sun 1 , Liang Zhu 1 , Zhao-Liang Sun 1 , Dong-Fu Feng 2
Affiliation  

Our recent study investigated the role of collapsin response mediator protein-2 (CRMP2) on dendritic spine morphology and memory function after traumatic brain injury (TBI). First, we examined the density and morphology of dendritic spines in Thy1-GFP mice on the 1 st day (P1D) and 7th day (P7D) after controlled cortical impact injury (CCI). The dendritic spine density in the hippocampus was decreased on P1D, in which mainly mushroom-type and thin-type spines were lost. The density of dendritic spines was increased on P7D, most of which were of the thin type. Next, we explored the expression of CRMP2 on P1D and P7D. CRMP2 expression was decreased on P1D, but the levels of the CRMP2 breakdown product were increased. On P7D, the expression pattern was the opposite. Then, we constructed CRMP2 overexpression and knockdown plasmids and transfected them into cultured neurons in vitro. CRMP2 increased the dendritic spine density of cultured neurons and the proportion of mushroom-type spines, while CRMP2-shRNA reduced the dendritic spine density and the proportion of mushroom-type spines. To determine the role of CRMP2 in dendritic spines after TBI, we stereotactically injected the CRMP2 overexpression and knockdown viruses into the hippocampus and found that CRMP2 increased the dendritic spine density and the proportion of mushroom-type spines after TBI. Meanwhile, as suggested by the morphological changes, fear conditioning behavioral experiments confirmed that CRMP2 improved memory deficits after TBI.

中文翻译:

CRMP2通过增强脑外伤后神经元树突棘的成熟来改善记忆缺陷。

我们最近的研究调查了胶原蛋白反应介导蛋白2(CRMP2)在脑外伤(TBI)后对树突棘形态和记忆功能的作用。首先,我们在控制皮质撞击损伤(CCI)后第1天(P1D)和第7天(P7D)检查了Thy1-GFP小鼠中树突棘的密度和形态。在P1D上海马的树突棘密度降低,其中主要丢失了蘑菇型和薄型棘。在P7D上树突棘的密度增加了,其中大多数是薄型的。接下来,我们探讨了CRMP2在P1D和P7D上的表达。在P1D上CRMP2的表达降低,但是CRMP2分解产物的水平增加。在P7D上,表达模式相反。然后,我们构建了CRMP2过表达和敲低质粒,并将其转染到体外培养的神经元中。CRMP2增加了培养的神经元的树突棘密度和蘑菇型棘的比例,而CRMP2-shRNA降低了树突棘密度和蘑菇型棘的比例。为了确定CRMP2在TBI后的树突棘中的作用,我们将CRMP2过表达和敲低病毒立体定向注入海马,发现CRMP2在TBI后增加了树突棘密度和蘑菇型棘突的比例。同时,正如形态变化所暗示的那样,恐惧条件行为实验证实了CRMP2改善了TBI后的记忆缺陷。CRMP2增加了培养的神经元的树突棘密度和蘑菇型棘的比例,而CRMP2-shRNA降低了树突棘密度和蘑菇型棘的比例。为了确定CRMP2在TBI后的树突棘中的作用,我们将CRMP2过表达和敲低病毒立体定向注入海马,发现CRMP2在TBI后增加了树突棘密度和蘑菇型棘突的比例。同时,正如形态变化所暗示的那样,恐惧条件行为研究证实,CRMP2改善了TBI后的记忆缺陷。CRMP2增加了培养的神经元的树突棘密度和蘑菇型棘的比例,而CRMP2-shRNA降低了树突棘密度和蘑菇型棘的比例。为了确定CRMP2在TBI后的树突棘中的作用,我们将CRMP2过表达和敲低病毒立体定向注入海马,发现CRMP2在TBI后增加了树突棘密度和蘑菇型棘突的比例。同时,正如形态变化所暗示的那样,恐惧条件行为实验证实了CRMP2改善了TBI后的记忆缺陷。我们从立体定位上将CRMP2过表达和敲低病毒注入海马中,发现CRMP2增加了TBI后的树突棘密度和蘑菇型棘突的比例。同时,正如形态变化所暗示的那样,恐惧条件行为实验证实了CRMP2改善了TBI后的记忆缺陷。我们从立体定位上将CRMP2过表达和敲低病毒注入海马中,发现CRMP2增加了TBI后的树突棘密度和蘑菇型棘突的比例。同时,正如形态变化所暗示的那样,恐惧条件行为实验证实了CRMP2改善了TBI后的记忆缺陷。
更新日期:2020-02-20
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