Progesterone treatment following traumatic brain injury in the 11-day-old rat attenuates cognitive deficits and neuronal hyperexcitability in adolescence.
Progesterone treatment following traumatic brain injury in the 11-day-old rat attenuates cognitive deficits and neuronal hyperexcitability in adolescence.
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DOI：
10.1016/j.expneurol.2020.113329
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发表时间：
2020-08
影响因子：
5.3
通讯作者：
Raghupathi R
中科院分区：
文献类型：
--
作者：
Lengel D;Huh JW;Barson JR;Raghupathi R
4岁以下儿童的创伤性脑损伤（TBI）导致青少年和成年期的认知和心理社会缺陷。在出生后第11天闭合性头部损伤后4周，雄性和雌性大鼠表现出新物体识别记忆（NOR）受损，沿着高架十字迷宫（高架十字迷宫）中开放臂时间增加，提示冒险行为。这是伴随着增加的内在兴奋性和自发兴奋性突触后电流（EPSC）的频率，和自发抑制性突触后电流的频率在内侧前额叶皮层（PFC），一个区域，涉及在对象识别和冒险行为的2/3层神经元的减少。脑损伤后第一周用孕酮治疗改善了假手术和脑损伤大鼠在4周时间点的NOR记忆，并另外减弱了损伤诱导的神经元兴奋性增加和自发EPSC的频率。孕酮对损伤后细胞兴奋性变化的影响可能与其降低假手术和脑损伤动物中内侧PFC中电压门控钠通道β3亚基的mRNA表达和增加神经元兴奋性氨基酸转运蛋白3的表达以及增加假手术而非脑损伤动物中谷氨酸脱羧酶mRNA表达的能力有关。预后治疗并不影响损伤引起的变化，在抗抑郁试验。这些结果表明，在11日龄大鼠TBI后立即给予孕酮可降低青春期的认知缺陷，这可能是由孕酮介导的调节内侧PFC内的兴奋性信号传导机制介导的。
Traumatic brain injury (TBI) in children younger than 4 years old results in cognitive and psychosocial deficits in adolescence and adulthood. At 4 weeks following closed head injury on postnatal day 11, male and female rats exhibited impairment in novel object recognition memory (NOR) along with an increase in open arm time in the elevated plus maze (EPM), suggestive of risk-taking behaviors. This was accompanied by an increase in intrinsic excitability and frequency of spontaneous excitatory post-synaptic currents (EPSCs), and a decrease in the frequency of spontaneous inhibitory post-synaptic currents in layer 2/3 neurons within the medial prefrontal cortex (PFC), a region that is implicated in both object recognition and risk-taking behaviors. Treatment with progesterone for the first week after brain injury improved NOR memory at the 4-week time point in both sham and brain-injured rats and additionally attenuated the injury-induced increase in the excitability of neurons and the frequency of spontaneous EPSCs. The effect of progesterone on cellular excitability changes after injury may be related to its ability to decrease the mRNA expression of the β3 subunit of the voltage-gated sodium channel and increase the expression of the neuronal excitatory amino acid transporter 3 in the medial PFC in sham- and brain-injured animals and also increase glutamic acid decarboxylase mRNA expression in sham- but not brain-injured animals. Progesterone treatment did not affect injury-induced changes in the EPM test. These results demonstrate that administration of progesterone immediately after TBI in 11-day-old rats reduces cognitive deficits in adolescence, which may be mediated by progesterone-mediated regulation of excitatory signaling mechanisms within the medial PFC.
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DOI：
10.1523/jneurosci.3572-11.2011
发表时间：
2011-10-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ding MC;Wang Q;Lo EH;Stanley GB
通讯作者：
Stanley GB
影响因子：
3.7
作者：
Geddes RI;Peterson BL;Stein DG;Sayeed I
通讯作者：
Sayeed I
影响因子：
2.7
作者：
Frye, Cheryl A.;Duffy, Caryn K.;Walf, Alicia A.
通讯作者：
Walf, Alicia A.
神经类固醇硫酸脱氢表雄酮通过激活 sigma-1 受体抑制大鼠内侧前额叶皮层的持续钠电流
影响因子：
5.3
作者：
Cheng, Zheng-Xiang;Lan, Dan-Mei;Zheng, Ping
通讯作者：
Zheng, Ping
影响因子：
4.2
作者：
Brizuela, Mariana;Blizzard, Catherine A.;Dickson, Tracey
通讯作者：
Dickson, Tracey