Stimulation of Anterior Thalamic Nuclei Protects Against Seizures and Neuronal Apoptosis in Hippocampal CA3 Region of Kainic Acid-induced Epileptic Rats.
Stimulation of Anterior Thalamic Nuclei Protects Against Seizures and Neuronal Apoptosis in Hippocampal CA3 Region of Kainic Acid-induced Epileptic Rats.
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DOI：
10.4103/0366-6999.179799
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发表时间：
2016-04-20
影响因子：
6.1
通讯作者：
Zhang JG
中科院分区：
文献类型：
--
作者：
Meng DW;Liu HG;Yang AC;Zhang K;Zhang JG
丘脑前核（ANT）刺激的抗癫痫作用已被证实；然而，其潜在机制尚不清楚。本研究旨在探讨慢性ANT刺激对海马神经元丢失和凋亡的影响。将64只大鼠分为4组：对照组、kainic acid （KA）组、模拟深部脑刺激（DBS）组和DBS组。KA用于诱导癫痫。计算癫痫发作次数和首次自发发作的潜伏期。采用尼氏染色法分析海马神经元丢失情况。采用聚合酶链反应和Western blotting检测海马CA3区caspase-3 （Casp3）、b细胞淋巴瘤-2 （Bcl2）和Bcl2相关X蛋白（Bax）的表达。采用单因素方差分析确定四组间的差异。DBS组首次自发发作潜伏期明显长于KA组（27.50±8.05∶16.38±7.25,P = 0.0005）。DBS组癫痫总发作次数明显减少（DBS组比KA组：11.75±6.80比23.25±7.72,P = 0.0002）。慢性抗-DBS可减少海马CA3区神经元损失（DBS组与KA组比较：23.58±6.34比13.13±4.00,P = 0.0012）。慢性DBS后，Casp3 mRNA相对表达量降低（DBS组比KA组：1.18±0.37比2.09±0.46,P = 0.0003）， Bcl2 mRNA相对表达量升高（DBS组比KA组：0.92±0.21比0.48±0.16,P = 0.0004）。DBS组CASP3蛋白表达水平（DBS组比KA组：1.25±0.26比2.49±0.38,P < 0.0001）和BAX蛋白表达水平（DBS组比KA组：1.57±0.49比2.80±0.63,P = 0.0012）均下降，BCL2蛋白表达水平（DBS组比KA组：0.78±0.32比0.36±0.17,P = 0.0086）升高。本研究表明，慢性ANT刺激对海马神经元具有神经保护作用。这种神经保护作用可能是通过抑制癫痫海马细胞凋亡介导的。
The antiepileptic effect of the anterior thalamic nuclei (ANT) stimulation has been demonstrated; however, its underlying mechanism remains unclear. The aim of this study was to investigate the effect of chronic ANT stimulation on hippocampal neuron loss and apoptosis. Sixty-four rats were divided into four groups: The control group, the kainic acid (KA) group, the sham-deep brain stimulation (DBS) group, and the DBS group. KA was used to induce epilepsy. Seizure count and latency to the first spontaneous seizures were calculated. Nissl staining was used to analyze hippocampal neuronal loss. Polymerase chain reaction and Western blotting were conducted to assess the expression of caspase-3 (Casp3), B-cell lymphoma-2 (Bcl2), and Bcl2-associated X protein (Bax) in the hippocampal CA3 region. One-way analysis of variance was used to determine the differences between the four groups. The latency to the first spontaneous seizures in the DBS group was significantly longer than that in the KA group (27.50 ± 8.05 vs. 16.38 ± 7.25 days, P = 0.0005). The total seizure number in the DBS group was also significantly reduced (DBS vs. KA group: 11.75 ± 6.80 vs. 23.25 ± 7.72, P = 0.0002). Chronic ANT-DBS reduced neuronal loss in the hippocampal CA3 region (DBS vs. KA group: 23.58 ± 6.34 vs. 13.13 ± 4.00, P = 0.0012). After chronic DBS, the relative mRNA expression level of Casp3 was decreased (DBS vs. KA group: 1.18 ± 0.37 vs. 2.09 ± 0.46, P = 0.0003), and the relative mRNA expression level of Bcl2 was increased (DBS vs. KA group: 0.92 ± 0.21 vs. 0.48 ± 0.16, P = 0.0004). The protein expression levels of CASP3 (DBS vs. KA group: 1.25 ± 0.26 vs. 2.49 ± 0.38, P < 0.0001) and BAX (DBS vs. KA group: 1.57 ± 0.49 vs. 2.80 ± 0.63, P = 0.0012) both declined in the DBS group whereas the protein expression level of BCL2 (DBS vs. KA group: 0.78 ± 0.32 vs. 0.36 ± 0.17, P = 0.0086) increased in the DBS group. This study demonstrated that chronic ANT stimulation could exert a neuroprotective effect on hippocampal neurons. This neuroprotective effect is likely to be mediated by the inhibition of apoptosis in the epileptic hippocampus.