Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin 682 022, Kerala, India.
Brain Res Bull. 2010 Apr 29;82(1-2):87-94. doi: 10.1016/j.brainresbull.2010.02.005. Epub 2010 Feb 17.
Oxidative stress plays an important role in cerebellar damage caused by diabetes, leading to deterioration in glucose homeostasis causing metabolic disorders. The present study was carried out to find the effects of Aegle marmelose leaf extract and insulin alone and in combination with pyridoxine on the cerebellar 5-HT through 5-HT(2A) receptor subtype, gene expression studies on the status of antioxidants-superoxide dismutase (SOD), glutathione peroxidase (GPx), 5-HT(2A) and 5-HT transporter (5-HTT) and immunohistochemical studies in streptozotocin induced diabetic rats. 5-HT and 5-HT(2A) receptor binding parameters, B(max) and K(d), showed a significant decrease (p<0.001) in the cerebellum of diabetic rats compared to control. Gene expression studies of SOD, GPx, 5-HT(2A) and 5-HTT in cerebellum showed a significant down regulation (p<0.001) in diabetic rats compared to control. Pyridoxine treated alone and in combination with insulin, A. marmelose to diabetic rats reversed the B(max), K(d) of 5-HT, 5-HT(2A) and the gene expression of SOD, GPx, 5-HT(2A) and 5-HTT in cerebellum to near control. The gene expression of 5-HT(2A) and 5-HTT were confirmed by immunohistochemical studies. Also, the Rotarod test confirms the motor dysfunction and recovery by treatment. These data suggest the antioxidant and neuroprotective role of pyridoxine and A. marmelose through the up regulation of 5-HT through 5-HT(2A) receptor in diabetic rats. Our results suggest that pyridoxine treated alone and in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalizing diabetic related oxidative stress and neurodegeneration affecting the motor ability of an individual by serotonergic receptors through 5-HT(2A) function. This has clinical significance in the management of diabetes.
氧化应激在糖尿病引起的小脑损伤中起着重要作用，导致葡萄糖稳态恶化，引起代谢紊乱。本研究旨在寻找芒果叶提取物和胰岛素单独及与吡哆醇联合应用对小脑 5-HT 通过 5-HT(2A)受体亚型的影响，研究抗氧化剂-超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）、5-HT(2A)和 5-HT 转运体（5-HTT）的基因表达状态，并在链脲佐菌素诱导的糖尿病大鼠中进行免疫组织化学研究。与对照组相比，糖尿病大鼠小脑 5-HT 和 5-HT(2A)受体结合参数 B(max)和 K(d)显著降低（p<0.001）。小脑 SOD、GPx、5-HT(2A)和 5-HTT 的基因表达研究表明，与对照组相比，糖尿病大鼠的基因表达显著下调（p<0.001）。吡哆醇单独和与胰岛素联合治疗、芒果叶提取物治疗糖尿病大鼠，使小脑 5-HT、5-HT(2A)的 B(max)、K(d)和 SOD、GPx、5-HT(2A)和 5-HTT 的基因表达恢复到接近对照组的水平。通过免疫组织化学研究证实了 5-HT(2A)和 5-HTT 的基因表达。此外，旋转棒试验证实了治疗后的运动功能障碍和恢复。这些数据表明，吡哆醇和芒果叶提取物通过上调 5-HT 通过 5-HT(2A)受体在糖尿病大鼠中发挥抗氧化和神经保护作用。我们的结果表明，吡哆醇单独和与胰岛素和芒果叶提取物联合治疗在调节胰岛素合成和释放、正常化糖尿病相关氧化应激和神经退行性变方面发挥作用，通过 5-HT(2A)功能影响个体的运动能力。这在糖尿病的管理中具有临床意义。
