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激活PV阳性抑制性神经元对脑缺血引起记忆障碍的改善作用
Improvement of activation of parvalbumin positive inhibitory neurons to memory impairment caused by frontal cortex ischemia
- 陆军军医大学学报 2022年44卷第10期 页码：984-990
- 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：
[穆建坤，E-mail：234630639@qq.com MU Jiankun, E-mail: 234630639@qq.com
- 基金信息：国家自然科学基金面上项目(81873755)
DOI：10.16016/j.2097-0927.202110197
中图分类号： R363.22;R743.31;R749.13收稿：2021-10-30，
修回：2022-01-09，
纸质出版：2022-05-30
- 稿件说明：
移动端阅览
刘畅, 王若兰, 胡俊, 等. 激活PV阳性抑制性神经元对脑缺血引起记忆障碍的改善作用[J]. 陆军军医大学学报, 2022,44(10):984-990.
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.
刘畅, 王若兰, 胡俊, 等. 激活PV阳性抑制性神经元对脑缺血引起记忆障碍的改善作用[J]. 陆军军医大学学报, 2022,44(10):984-990. DOI： 10.16016/j.2097-0927.202110197.
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
2
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
2
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
2
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(
P
<
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(
P
<
0.05)，提高在物体位置识别任务中的探索分数(
P
<
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
2
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
2
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
2
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
2
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 (
P
<
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 (
P
<
0.05) and the exploration score in object location and recognition tasks (
P
<
0.05).
Conclusion
2
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
LIVINGSTON-THOMAS J M, JEFFERS M S, NGUEMENI C, et al . Assessing cognitive function following medial prefrontal stroke in the rat[J ] . Behav Brain Res, 2015, 294: 102-110. DOI: 10.1016/j.bbr.2015.07.053.
QÜ M, MITTMANN T, LUHMANN H J, et al . Long-term changes of ionotropic glutamate and GABA receptors after unilateral permanent focal cerebral ischemia in the mouse brain[J ] . Neuroscience, 1998, 85(1): 29-43. DOI: 10.1016/s0306-4522(97)00656-8.
ZHOU L Y Y, WRIGHT T E, CLARKSON A N. Prefrontal cortex stroke induces delayed impairment in spatial memory[J]. Behav Brain Res, 2016, 296: 373-378. DOI: 10.1016/j.bbr.2015.08.022.
TREMBLAY R, LEE S, RUDY B. GABAergic interneurons in the neocortex: from cellular properties to circuits[J]. Neuron, 2016, 91(2): 260-292. DOI: 10.1016/j.neuron.2016.06.033.
IACCARINO H F, SINGER A C, MARTORELL A J, et al . Gamma frequency entrainment attenuates amyloid load and modifies microglia[J ] . Nature, 2016, 540(7632): 230-235. DOI: 10.1038/nature20587.
CHEN L, HU J, MU J K, et al . Specific stimulation of PV+ neurons at early stage ameliorates prefrontal ischemia-induced spatial working memory impairment[J ] . Behav Brain Res, 2021, 414: 113511. DOI: 10.1016/j.bbr.2021.113511.
SAIKA F, MATSUZAKI S, KISHIOKA S, et al . Chemogenetic activation of CX3CR1-expressing spinal microglia using gq-DREADD elicits mechanical allodynia in male mice[J ] . Cells, 2021, 10(4): 874. DOI: 10.3390/cells10040874.
ALLEN D C, JIMENEZ V A, CARLSON T L, et al . Characterization of DREADD receptor expression and function in rhesus macaques trained to discriminate ethanol[J ] . Neuropsychopharmacology, 2021: 1-9. DOI: 10.1038/s41386-021-01181-5.
KHAMBHATI A N, BASSETT D S. A powerful DREADD: revealing structural drivers of functional dynamics[J]. Neuron, 2016, 91(2): 213-215. DOI: 10.1016/j.neuron.2016.07.011.
GOMEZ J L, BONAVENTURA J, LESNIAK W, et al . Chem-ogenetics revealed: DREADD occupancy and activation via converted clozapine[J ] . Science, 2017, 357(6350): 503-507. DOI: 10.1126/science.aan2475..
DÉZIEL R A, RYAN C L, TASKER R A. Ischemic lesions localized to the medial prefrontal cortex produce selective deficits in measures of executive function in rats[J]. Behav Brain Res, 2015, 293: 54-61. DOI: 10.1016/j.bbr.2015.07.003.
HAZELL A S. Excitotoxic mechanisms in stroke: an update of concepts and treatment strategies[J]. Neurochem Int, 2007, 50(7/8): 941-953. DOI: 10.1016/j.neuint.2007.04.026.
ERDEMLI G, CRUNELLI V. Response of thalamocortical neurons to hypoxia: a whole-cell patch-clamp study[J]. J Neurosci, 1998, 18(14): 5212-5224. DOI: 10.1523/jneurosci.18-14-05212.1998.
KRNJEVIĆK. Electrophysiology of cerebral ischemia[J]. Neuropharmacology, 2008, 55(3): 319-333. DOI: 10.1016/j.neuropharm.2008.01.002.
CALABRESI P, PISANI A, MERCURI N B, et al . Hypoxia-induced electrical changes in striatal neurons[J ] . J Cereb Blood Flow Metab, 1995, 15(6): 1141-1145. DOI: 10.1038/jcbfm.1995.142.
CHEN X, ZHANG J, SONG Y, et al . Deficiency of anti-inflammatory cytokine IL-4 leads to neural hyperexcitability and aggravates cerebral ischemia-reperfu sion injury[J ] . Acta Pharm Sin B, 2020, 10(9): 1634-1645. DOI: 10.1016/j.apsb.2020.05.002.
SONG H, MYLVAGANAM S M, WANG J, et al . Contributions of the hippocampal CA3 circuitry to acute seizures and hyperexcitability responses in mouse models of brain ischemia[J ] . Front Cell Neurosci, 2018, 12: 278. DOI: 10.3389/fncel.2018.00278.
GŁODZIK-SOBA ŃSKA L, SŁOWIK A, KOZUB J, et al . GABA in ischemic stroke. Proton magnetic resonance study[J ] . Med Sci Monit, 2004, 10 (Suppl 3): 88-93.
KRIMER L S, GOLDMAN-RAKIC P S. Prefrontal microcircuits: membrane properties and excitatory input of local, medium, and wide Arbor interneurons[J]. J Neurosci, 2001, 21(11): 3788-3796. DOI: 10.1523/jneurosci.21-11-03788.2001.
COSTA J F, DINES M, LAMPRECHT R. The role of rac GTPase in dendritic spine morphogenesis and memory[J]. Front Synaptic Neurosci, 2020, 12: 12. DOI: 10.3389/fnsyn.2020.00012.
MAS R, ZUO Y. Synaptic modifications in learning and memory—a dendritic spine story[J]. Semin Cell Dev Biol, 2021. DOI: 10.1016/j.semcdb.2021.05.015.
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