The Role of 5-HTR6 in Mossy Fiber Sprouting: Activating Fyn and p-ERK1/2 in Pilocarpine-Induced Chronic Epileptic Rats
The Role of 5-HTR6 in Mossy Fiber Sprouting: Activating Fyn and p-ERK1/2 in Pilocarpine-Induced Chronic Epileptic Rats
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5-HTR6 在苔藓纤维发芽中的作用：在毛果芸香碱诱导的慢性癫痫大鼠中激活 Fyn 和 p-ERK1/2
DOI：
10.1159/000477322
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发表时间：
2017-05
影响因子：
--
通讯作者：
Huang Huapin
中科院分区：
文献类型：
--
作者：
Lin Wanhui;Huang Wenli;Chen Shenggen;Lin Mingxing;Huang Qingyu;Huang Huapin
目的：我们的主要目的是验证5-HTR 6是否参与苔藓纤维发芽（MFS）的发展，并确定MFS的进展是如何受到5-HTR 6的影响。方法：90只成年雄性SD大鼠随机分为对照组（n=36）和癫痫组（n=54）。采用腹腔注射（i. p.）注射氯化锂-毛果芸香碱。我们分两个阶段进行实验。第一阶段包括将36只癫痫大鼠等分为三组，分别给予无治疗组、5-HTR 6拮抗剂SB-27104（SB）治疗组和溶媒DMSO治疗组。采用视频脑电图（video-EEG）监测大鼠行为学和脑电图（EEG）。第二阶段包括将126只癫痫大鼠分为7组，分别给予无、10%DMSO、SB（100 µg/kg）、Fyn拮抗剂PP 2（50 µg/kg）、p-ERK 1/2拮抗剂PD-98059（30 µg/kg）、SB（100 µg/ kg）+PP 2（50 µg/kg）、SB（100 µ g/kg）+ PD-98059（30 µg/kg）治疗。我们还用100 μg/kg 5-HTR 6激动剂WAY-181187（WAY）治疗了第一阶段对照组中的18只大鼠。采用Timm染色法检测大鼠MFS。最后，通过Western印迹或RT-PCR对5-HTR 6、Fyn、p-ERK 1/2和GAP-3的表达进行定性和半定量。结果：SE诱导可刺激MFS形成，并增加GAP-43的表达。5-HTR 6、Fyn和p-ERK 1/2的表达也随着SE模型建立后时间的延长而上调。SB、PP 2和PD对MFS的形成有明显的抑制作用。与单一拮抗剂相比，SB+PD或SB+PP的抑制作用增强。WAY可上调Fyn和p-ERK 1/2的表达，促进MFS的发生（P < 0.05）。抑制Fyn后，p-ERK 1/2表达呈下调趋势（P < 0.05），而抑制p-ERK 1/2对Fyn表达无明显影响。结论：HTR 6可能通过激活p-ERK 1/2和Fyn，进而调节GAP-43的表达，影响MFS的进展。
Objective: Our primary objective is to verify whether 5-HTR6 is involved in the development of mossy fiber sprouting (MFS), and to determine how the progression of MFS is affected by 5-HTR6. Methods: A total of 90 male adult Sprague-Dawley rats were allocated into either the control group (n=36) or the epileptic group (n=54). Status epilepticus (SE) of rats was induced by the intraperitoneal (i.p.) injection of LiCl-pilocarpine. We conducted our experiments in two stages. The first stage involves equally dividing 36 epileptic rats into three groups with treatments of none, 5-HTR6 antagonist SB-27104 (SB) and vehicle DMSO. Then behavior and electroencephalogram (EEG) of rats were monitored by video-EEG. The second stage involves dividing 126 epileptic rats into seven groups with treatments of none, 10% DMSO, SB (100 µg/kg), Fyn antagonist PP2 (50 µg/kg), p-ERK1/2 antagonist PD-98059 (30 µg/kg), SB (100 µg/ kg) + PP2 (50 µg/kg); SB (100 µg/kg) + PD-98059 (30 µg/kg). We also treated 18 rats in the control group of the first stage with 100 µg/kg 5-HTR6 agonist WAY-181187 (WAY). MFS of rats was detected through the approach of Timm’s staining. Finally, expressions of 5-HTR6, Fyn, p-ERK1/2 and GAP-3 were qualified and semi-quantified via western blotting or RT-PCR. Results: Induction of SE could stimulate formation of MFS and increased GAP-43 expressions. Expressions of 5-HTR6, Fyn and p-ERK1/2 were also up-regulated with increasing time after establishment of SE models. The development of MFS was remarkably inhibited by SB, PP2 and PD. Compared to the single antagonist, such an inhibitory effect was enhanced by SB+PD or SB+PP. Moreover, treatment of healthy rats with WAY would contribute to up-regulated Fyn and p-ERK1/2 expressions, as well as development of MFS (P < 0.05). Suppression of Fyn triggered a down-regulating trend of p-ERK1/2 (P < 0.05), however, suppressed p-ERK1/2 did not have such a significant effect on Fyn expression. Conclusion: HTR6 may affect the progression of MFS by activating both p-ERK1/2 and Fyn, which further modulate the expression of GAP-43.
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影响因子：
16.6
作者：
Freir, Darragh B.;Nicoll, Andrew J.;Klyubin, Igor;Panico, Silvia;Mc Donald, Jessica M.;Risse, Emmanuel;Asante, Emmanuel A.;Farrow, Mark A.;Sessions, Richard B.;Saibil, Helen R.;Clarke, Anthony R.;Rowan, Michael J.;Walsh, Dominic M.;Collinge, John
通讯作者：
Collinge, John
影响因子：
3.7
作者：
Lee CY;Jaw T;Tseng HC;Chen IC;Liou HH
通讯作者：
Liou HH
影响因子：
3.4
作者：
Carr, Gregory V.;Lucki, Irwin
通讯作者：
Lucki, Irwin
DOI：
10.1152/ajpcell.00617.2005
发表时间：
2006-12
期刊：
American journal of physiology. Cell physiology
影响因子：
--
作者：
Michael D. Godeny;P. Sayeski
通讯作者：
Michael D. Godeny;P. Sayeski
影响因子：
2.5
作者：
Lin, Wan-hui;Huang, Hua-pin;Lin, Ji-lan
通讯作者：
Lin, Ji-lan