Garcinol Upregulates GABAA and GAD65 Expression, Modulates BDNF-TrkB Pathway to Reduce Seizures in Pentylenetetrazole (PTZ)-Induced Epilepsy.
Garcinol Upregulates GABAA and GAD65 Expression, Modulates BDNF-TrkB Pathway to Reduce Seizures in Pentylenetetrazole (PTZ)-Induced Epilepsy.
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DOI：
10.12659/msm.897579
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发表时间：
2016-11-17
期刊：
影响因子：
--
通讯作者：
Liu XW
中科院分区：
文献类型：
--
作者：
Hao F;Jia LH;Li XW;Zhang YR;Liu XW
癫痫是以反复发作为特征的最主要的神经系统疾病。尽管使用抗癫痫药物治疗，但由于药物的相关不良反应，癫痫仍然是一个治疗的挑战。以往的研究表明，脑源性神经营养因子-TrkB信号通路以及谷氨酸脱羧酶65(GAD65)和GABAA在癫痫发病中的重要作用。因此，能够调节BDNF-TrkB信号和GAD65和GABAA表达的药物可能有助于治疗。最近的实验数据集中在治疗中的植物衍生化合物上。藤黄酚，又称藤黄醇，是从藤黄果实中提取的一种聚异戊二烯基二苯甲酮。在戊四氮(PTZ)诱导的癫痫模型中，我们观察了藤黄酚的作用。癫痫点燃小鼠的癫痫评分被测量。尼氏染色、原位末端标记法和荧光Jade B染色检测神经元变性和凋亡。免疫组织化学方法检测caspase-3裂解产物的表达。免疫印迹法检测BDNF、TrkB、GABAA、GAD65、Bad、Bcl2、Bclxl、Bax的表达。用肌醇预处理可显著降低癫痫发作评分和死亡率。熊果酚可有效下调点燃小鼠脑内凋亡蛋白和caspase-3的表达。致痫小鼠脑源性神经营养因子和TrkB表达增加，GABAA和GAD65表达显著降低。肉桂酚显著增强GABAA和GAD65，抑制BDNF和TrkB。肉桂酚可提高小鼠在Morris水迷宫实验中的表现。肉桂酚通过抑制细胞凋亡，调节BDNF-TrkB信号和GAD65/GABAA的表达，发挥神经保护作用，并增强小鼠的认知和记忆。
Epilepsy is the most predominant neurological disorder characterized by recurrent seizures. Despite treatment with antiepileptic drugs, epilepsy still is a challenge to treat, due to the associated adverse effects of the drugs. Previous investigations have shown critical roles of BDNF-TrkB signalling and expression of glutamic acid decarboxylase 65 (GAD65) and GABAA in the brain during epilepsy. Thus, drugs that could modulate BDNF-TrkB signal and expression of GAD65 and GABAA could aid in therapy. Recent experimental data have focussed on plant-derived compounds in treatments. Garcinol (camboginol), is a polyisoprenylated benzophenone derived from the fruit of Garcinia indica. We investigated the effects of garcinol in pentylenetetrazole (PTZ)-induced epileptic models. Seizure scores were measured in epilepsy kindled mice. Neuronal degeneration and apoptosis were assessed by Nissl staining, TUNEL assay, and Fluoro-Jade B staining. Immunohistochemistry was performed to evaluate cleaved caspase-3 expressions. Expression of BDNF, TrkB, GABAA, GAD65, Bad, Bcl-2, Bcl-xL, and Bax were determined by western blots. Significantly reduced seizure scores and mortality rates were observed with pretreatment with garcinol. Elevated expression of apoptotic proteins and caspase-3 in kindled mice were effectively downregulated by garcinol. Epileptogenic mice presented increased BDNF and TrkB with considerably decreased GABAA and GAD65 expression. Garcinol significantly enhanced GABAA and GAD65 while it suppressed BDNF and TrkB. Garcinol enhanced the performance of mice in Morris water maze tests. Garcinol exerts neuroprotective effects via supressing apoptosis and modulating BDNF-TrkB signalling and GAD65/GABAA expressions and also enhanced cognition and memory of the mice.
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DOI：
10.1080/01635581.2012.718032
发表时间：
2012
期刊：
Nutrition and cancer
影响因子：
--
作者：
Chen X;Zhang X;Lu Y;Shim JY;Sang S;Sun Z;Chen X
通讯作者：
Chen X
影响因子：
3.5
作者：
DIEMER, NH;JORGENSEN, MB;HONORE, T
通讯作者：
HONORE, T
影响因子：
6.3
作者：
BENVENISTE, H;JORGENSEN, MB;DIEMER, NH
通讯作者：
DIEMER, NH
影响因子：
6.1
作者：
Cheng, An-Chin;Tsai, Mei-Ling;Pan, Min-Hsiung
通讯作者：
Pan, Min-Hsiung
影响因子：
4.2
作者：
Dos-Anjos, Severiano;Martinez-Villayandre, Beatriz;Fernandez-Lopez, Arsenio
通讯作者：
Fernandez-Lopez, Arsenio