Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin - 682 022, Kerala, India.
J Biomed Sci. 2010 Feb 5;17(1):7. doi: 10.1186/1423-0127-17-7.
Glucose homeostasis in humans is an important factor for the functioning of nervous system. Hypoglycemia and hyperglycemia is found to be associated with central and peripheral nerve system dysfunction. Changes in acetylcholine receptors have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS). In the present study we showed the effects of insulin induced hypoglycemia and streptozotocin induced diabetes on the cerebellar cholinergic receptors, GLUT3 and muscle cholinergic activity. Results showed enhanced binding parameters and gene expression of Muscarinic M1, M3 receptor subtypes in cerebellum of diabetic (D) and hypoglycemic group (D + IIH and C + IIH). alpha7nAchR gene expression showed a significant upregulation in diabetic group and showed further upregulated expression in both D + IIH and C + IIH group. AchE expression significantly upregulated in hypoglycemic and diabetic group. ChAT showed downregulation and GLUT3 expression showed a significant upregulation in D + IIH and C + IIH and diabetic group. AchE activity enhanced in the muscle of hypoglycemic and diabetic rats. Our studies demonstrated a functional disturbance in the neuronal glucose transporter GLUT3 in the cerebellum during insulin induced hypoglycemia in diabetic rats. Altered expression of muscarinic M1, M3 and alpha7nAchR and increased muscle AchE activity in hypoglycemic rats in cerebellum is suggested to cause cognitive and motor dysfunction. Hypoglycemia induced changes in ChAT and AchE gene expression is suggested to cause impaired acetycholine metabolism in the cerebellum. Cerebellar dysfunction is associated with seizure generation, motor deficits and memory impairment. The results shows that cerebellar cholinergic neurotransmission is impaired during hyperglycemia and hypoglycemia and the hypoglycemia is causing more prominent imbalance in cholinergic neurotransmission which is suggested to be a cause of cerebellar dysfunction associated with hypoglycemia.
人类的血糖稳态是神经系统功能的重要因素。低血糖和高血糖被发现与中枢和周围神经系统功能障碍有关。乙酰胆碱受体的变化与许多中枢神经系统（CNS）主要疾病的病理生理学有关。在本研究中，我们研究了胰岛素诱导的低血糖和链脲佐菌素诱导的糖尿病对小脑胆碱能受体、GLUT3 和肌肉胆碱能活性的影响。结果表明，糖尿病（D）和低血糖组（D+IIH 和 C+IIH）小脑中 M1、M3 型毒蕈碱受体亚基的结合参数和基因表达增强。α7nAchR 基因表达在糖尿病组中显著上调，并在 D+IIH 和 C+IIH 组中进一步上调表达。AchE 表达在低血糖和糖尿病组中显著上调。ChAT 表达下调，GLUT3 表达在 D+IIH 和 C+IIH 以及糖尿病组中显著上调。低血糖和糖尿病大鼠肌肉中的 AchE 活性增强。我们的研究表明，在糖尿病大鼠胰岛素诱导的低血糖期间，神经元葡萄糖转运体 GLUT3 在小脑功能失调。小脑内低血糖大鼠 M1、M3 和 α7nAchR 表达改变和肌肉 AchE 活性增加提示认知和运动功能障碍。低血糖诱导的 ChAT 和 AchE 基因表达变化提示小脑乙酰胆碱代谢受损。小脑功能障碍与癫痫发作、运动缺陷和记忆障碍有关。结果表明，高血糖和低血糖时小脑胆碱能神经传递受损，低血糖导致胆碱能神经传递更明显失衡，提示与低血糖相关的小脑功能障碍的原因。
