Improvement of activation of parvalbumin positive inhibitory neurons to memory impairment caused by frontal cortex ischemia

Chang LIU; Ruolan WANG; Jun HU; Jiankun MU

doi:10.16016/j.2097-0927.202110197

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Improvement of activation of parvalbumin positive inhibitory neurons to memory impairment caused by frontal cortex ischemia

Neurosciences | 更新时间：2026-01-09

- Improvement of activation of parvalbumin positive inhibitory neurons to memory impairment caused by frontal cortex ischemia
- Journal of Army Medical University Vol. 44, Issue 10, Pages: 984-990(2022)
- 作者机构：
  
  1.400050 重庆，重庆医科大学附属康复医院神经康复科
  2.400038 重庆，陆军军医大学(第三军医大学)第一附属医院神经内科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81873755)
- DOI：10.16016/j.2097-0927.202110197
  CLC： R363.22;R743.31;R749.13
- Received：30 October 2021，
  
  Revised：2022-01-09，
  
  Published：30 May 2022
- 稿件说明：
移动端阅览
Chang LIU, Ruolan WANG, Jun HU, et al. Improvement of activation of parvalbumin positive inhibitory neurons to memory impairment caused by frontal cortex ischemia[J]. Journal of Army Medical University, 2022, 44(10): 984-990.
DOI：

Chang LIU, Ruolan WANG, Jun HU, et al. Improvement of activation of parvalbumin positive inhibitory neurons to memory impairment caused by frontal cortex ischemia[J]. Journal of Army Medical University, 2022, 44(10): 984-990. DOI： 10.16016/j.2097-0927.202110197.

摘要

目的

探讨激活小白蛋白(parvalbumin，PV)阳性抑制性神经元对额叶皮层缺血所致记忆功能障碍的影响，并分析其作用机制。

方法

采用随机数字表法，将成年PV-Cre小鼠分为3组：对照组[额叶皮层PV神经元表达hM3D-mCherry，额叶皮层注射0.9% NaCl溶剂+腹腔注射氯氮平(clozapine N-oxide hydrochloride

CNO)]、模型组(额叶皮层PV神经元表达mCherry，额叶皮层区注射内皮素+腹腔注射生理盐水)、干预组(额叶皮层PV神经元表达hM3D-mCherry，额叶皮层注射内皮素+腹腔注射CNO)。其中，通过病毒微量注射技术，使得模型组小鼠额叶皮层PV神经元特异表达mCherry，而对照组和干预组小鼠额叶皮层区PV神经元特异表达hM3D-mCherry。通过药物遗传学，在干预组注射CNO可通过hM3D特异激活PV阳性神经元。通过T-迷宫和物体位置识别检测小鼠的记忆和运动功能。应用高尔基染色分析额叶皮层区锥体神经元树突棘密度的改变。

结果

额叶皮层给予内皮素可引起局部缺血。与对照组比较，额叶皮层缺血后引起其锥体神经元上树突棘密度减少，造成小鼠在T-迷宫中选择正确率下降，在物体空间位置识别任务中探索分数降低(

0.01)。激活PV阳性神经元能够显著增加额叶皮层树突棘的密度，显著提高小鼠在T-迷宫中的选择正确率(

0.05)，提高在物体位置识别任务中的探索分数(

0.05)。激活额叶皮层PV阳性神经元并未影响动物运动功能。

结论

激活PV阳性神经元可改善额叶皮层缺血引起的记忆功能障碍，其可能与提高额叶皮层内树突棘密度有关。

Abstract

Objective

To determine the effect of activating parvalbumin (PV) positive inhibitory neurons on memory impairment caused by frontal cortex ischemia and analyze the related mechanism.

Methods

Adult PV-Cre mice were randomly divided into control group [frontal cortex injection of 0.9% NaCl+ intraperitoneal injection of clozapine N-oxide hydrochloride (CNO)]

model group (frontal cortex injection of endothelin+intraperitoneal injection of 0.9% NaCl) and intervention group (prefrontal cortex injection of endothelin+intraperitoneal injection of CNO). Among them

virus microinjection technology was adopted to specifically express mCherry in the PV neurons in the frontal cortex of mice from the control group

while specifically express hM3d-mCherry in the PV neurons from the model group and the intervention group. Injection of CNO was performed in the intervention group to specifically activate PV positive neurons through hM3d. The memory and motor functions of mice were detected by T-maze and object location and recognition tasks. The changes of dendritic spine density of pyramidal neurons in frontal cortex were analyzed by Golgi staining.

Results

The administration of endothelin in frontal cortex caused local ischemia. Compared with the normal control group

the density of dendritic spines on pyramidal neurons was decreased after frontal cortex ischemia

resulting in the decrease of selection accuracy in T-maze and exploration scores in object location and recognition tasks (

0.01). On the contrary

activation of PV positive neurons significantly increased the density of dendritic spines in frontal cortex

and significantly improved the selection accuracy of mice in T-maze test (

0.05) and the exploration score in object location and recognition tasks (

0.05).

Conclusion

Activation of PV positive neurons can improve memory impairment caused by frontal cortex ischemia

which may be related to increasing the density of dendritic spines in frontal cortex.

关键词

Keywords

references

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