Upregulation of GAD65 mRNA in the medulla of the rat model of metabolic syndrome
Upregulation of GAD65 mRNA in the medulla of the rat model of metabolic syndrome
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DOI：
10.1016/j.neulet.2007.04.042
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发表时间：
2007-05-29
影响因子：
2.5
通讯作者：
Watson, Stanlev J.
中科院分区：
文献类型：
--
作者：
Buck, Bradley J.;Kerman, Ilan A.;Watson, Stanlev J.
代谢综合征的特征是肥胖、血压升高、胰岛素抵抗和高胆固醇血症。最近，有人提出了一种这种疾病的动物模型，即根据老鼠在跑步机上跑步任务的表现选择性繁殖的老鼠。因此，与高能力跑步者 (HCR) 大鼠相比，低能力跑步者 (LCR) 大鼠表现出代谢综合征的所有诊断标准，包括血压升高 [U.维斯洛夫，S.M. Najjar, O. Ellingsen, P.M. Haram、S. Swoap、Q. Al-Share、M. Fernstrom、K. Rezaei、S.J.李，L.G.科赫，S.L. Britton，低有氧能力的人工选择后出现心血管危险因素，Science 307 (2005) 418-420]。先前的研究强调了 BR 中枢控制的髓质心血管调节区中 GABA 能神经传递的重要性，因此，我们假设 LCR 大鼠的髓质心血管调节核中 GABA 能传递失调。为了开始检验这一假设，我们进行了实验，通过放射性原位杂交检查两种大鼠品系中 GABA 合成酶、GAD65 和 GAD67 mRNA 的表达。我们的结果显示 GAD65 和 GAD67 mRNA 在整个脑干中广泛表达；定量显示，与 HCR 大鼠相比，LCR 动物尾侧孤束核 (NTS) 和头端腹外侧延髓 (VLM) 中的 GAD65 mRNA 表达增加。相反，在这些区域中未检测到 GAD67 表达的差异。这些数据与代谢综合征中 NTS 和 VLM 中 GABA 能神经传递改变的概念一致，并指出这些区域在心血管调节中的重要性。 (c) 2007 Elsevier Ireland Ltd. 保留所有权利。
Metabolic syndrome is characterized by obesity, elevated blood pressure (BP), insulin resistance, and hypercholesterolemia. Recently an animal model of this disorder has been proposed in rats selectively bred based on their performance on a treadmill-running task. Accordingly, low capacity runner (LCR) rats exhibited all of the diagnostic criteria for metabolic syndrome, including elevated BP, as compared to their high capacity runner (HCR) counterparts [U. Wisloff, S.M. Najjar, O. Ellingsen, P.M. Haram, S. Swoap, Q. Al-Share, M. Fernstrom, K. Rezaei, S.J. Lee, L.G. Koch, S.L. Britton, Cardiovascular risk factors emerge after artificial selection for low aerobic capacity, Science 307 (2005) 418-420]. Previous studies have highlighted the importance of GABAergic neurotransmission in the medullary cardiovascular-regulatory areas in the central control of BR Thus, we hypothesized a dysregulation in GABAergic transmission in the medullary cardiovascular-regulatory nuclei of LCR rats. To begin testing this hypothesis we carried out experiments examining expression of the GABA synthetic enzymes, GAD65 and GAD67, mRNAs in the two rat strains via radioactive in situ hybridization. Our results showed GAD65 and GAD67 mRNAs were widely expressed throughout the brainstem; quantification revealed increased GAD65 mRNA expression in LCR animals in the caudal nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (VLM) as compared to HCR rats. Conversely, no differences in the expression of GAD67 were detected in these regions. These data are consistent with the notion of altered GABAergic neurotransmission in the NTS and VLM in metabolic syndrome, and point to the importance of these regions in cardiovascular regulation. (c) 2007 Elsevier Ireland Ltd. All rights reserved.