Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: neuroprotective role of pyridoxine and Aegle marmelose.
Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: neuroprotective role of pyridoxine and Aegle marmelose.
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DOI：
10.1186/1423-0127-17-78
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发表时间：
2010-09-25
影响因子：
11
通讯作者：
Paulose CS
中科院分区：
文献类型：
--
作者：
Abraham PM;Kuruvilla KP;Mathew J;Malat A;Joy S;Paulose CS
糖尿病和应激刺激海马5-HT的合成、代谢和释放。本研究旨在探讨胰岛素、甘露聚糖单用及联用吡哆醇对链脲佐菌素诱导的糖尿病大鼠海马5-HT、5-HT2A受体亚型、5-HT2A、5-HTT基因表达研究、INSR、免疫组化研究及升高+迷宫的影响。与对照组相比，糖尿病大鼠海马5-HT含量显著降低（p < 0.001）， 5-HIAA含量显著升高（p < 0.001）。与对照组相比，5-HT受体结合参数Bmax和Kd显著降低（p < 0.001）， 5-HT2A受体结合参数Bmax显著降低（p < 0.001），海马Kd显著升高（p < 0.05）。海马5-HT2A、5-HTT和INSR基因表达研究显示，与对照组相比，糖尿病大鼠海马5-HT2A、5-HTT和INSR基因表达显著下调（p < 0.001）。吡哆醇联合胰岛素、麦芽糖治疗糖尿病大鼠后，海马组织5-HT含量、5-HT、5-HT2A的Bmax、Kd及5-HT2A、5- httt、INSR基因表达均恢复到接近控制水平。免疫组化研究证实5-HT2A和5-HTT基因表达。行为学研究表明，血清素通过其转运体显著增加了糖尿病大鼠的焦虑相关特征（p < 0.001），并通过联合治疗得到纠正。我们的研究结果表明，吡哆醇与胰岛素和麦芽糖联合治疗可以调节胰岛素的合成和释放，通过海马血清素能功能使糖尿病相关的应激和焦虑正常化。这对糖尿病的治疗具有临床意义。
Diabetes and stress stimulate hippocampal 5-HT synthesis, metabolism and release. The present study was carried out to find the effects of insulin, Aegle marmelose alone and in combination with pyridoxine on the hippocampal 5-HT, 5-HT2A receptor subtype, gene expression studies on 5-HT2A, 5-HTT, INSR, immunohistochemical studies and elevated plus maze in streptozotocin induced diabetic rats. 5-HT content showed a significant decrease (p < 0.001) and a significant increase (p < 0.001) in 5-HIAA in hippocampus of diabetic rats compared to control. 5-HT receptor binding parameters Bmax and Kd showed a significant decrease (p < 0.001) whereas 5-HT2A receptor binding parameters Bmax showed a significant decrease (p < 0.001) with a significant increase (p < 0.05) in Kd in hippocampus of diabetic rats compared to control. Gene expression studies of 5-HT2A, 5-HTT and INSR in hippocampus showed a significant down regulation (p < 0.001) in diabetic rats compared to control. Pyridoxine treated in combination with insulin and A. marmelose to diabetic rats reversed the 5-HT content, Bmax , Kd of 5-HT, 5-HT2A and gene expression of 5-HT2A, 5-HTT and INSR in hippocampus to near control. The gene expression of 5-HT2A and 5-HTT were confirmed by immunohistochemical studies. Behavioural studies using elevated plus maze showed that serotonin through its transporter significantly increased (p < 0.001) anxiety-related traits in diabetic rats which were corrected by combination therapy. Our results suggest that pyridoxine treated in combination with insulin and A. marmelose has a role in the regulation of insulin synthesis and release, normalising diabetic related stress and anxiety through hippocampal serotonergic function. This has clinical significance in the management of diabetes.
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影响因子：
8.3
作者：
Fujioka, M;Okuchi, K;Ishii, Y
通讯作者：
Ishii, Y
影响因子：
2.9
作者：
Miyata, Shigeo;Yamada, Naoko;Kamei, Junzo
通讯作者：
Kamei, Junzo
影响因子：
2.5
作者：
Abraham, Pretty Mary;Anju, T. R.;Paulose, C. S.
通讯作者：
Paulose, C. S.
影响因子：
4.7
作者：
GLOWINSKI, J;IVERSEN, LL
通讯作者：
IVERSEN, LL
影响因子：
2.7
作者：
GUIMARAES, FS;DELBEL, EA;DEALMEIDA, RT
通讯作者：
DEALMEIDA, RT