Telmisartan treatment ameliorates memory deficits in streptozotocin-induced diabetic mice via attenuating cerebral amyloidosis.
Telmisartan treatment ameliorates memory deficits in streptozotocin-induced diabetic mice via attenuating cerebral amyloidosis.
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DOI：
10.1254/jphs.13157fp
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发表时间：
2014-04
影响因子：
3.5
通讯作者：
G. Du;Meng Hu;Z. Mei;Chao Wang;G. Liu;Mei Hu;Yan Long;Ming-xing Miao;Jia Chang Li;H. Hon
中科院分区：
文献类型：
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作者：
G. Du;Meng Hu;Z. Mei;Chao Wang;G. Liu;Mei Hu;Yan Long;Ming-xing Miao;Jia Chang Li;H. Hon
据报告，替米沙坦是一种血管紧张素II 1型受体阻滞剂（ARB），对中枢神经系统（CNS）具有有益作用。然而，替米沙坦对1型糖尿病相关认知损害的影响尚不清楚。在这里，我们研究了替米沙坦可以改善1型糖尿病小鼠模型，链脲佐菌素（STZ）诱导的糖尿病小鼠的记忆功能的可能性。STZ诱导的糖尿病小鼠在Morris水迷宫（MWM）任务中表现出明显的空间学习和记忆能力下降。两种非水肿剂量（0.7或0.35 mg/kg）的替米沙坦经口给药可显著改善STZ诱导的糖尿病小鼠的记忆缺陷。与未治疗的糖尿病小鼠相比，替米沙坦治疗显著降低了STZ诱导的糖尿病小鼠海马和皮质的Aβ-淀粉样蛋白、APP、BACE 1、β-淀粉样蛋白和NF-κB p65，但对高血糖和低胰岛素血症没有有利影响。综上所述，我们的研究结果表明，替米沙坦改善1型糖尿病小鼠的记忆缺陷，至少部分是因为大脑中淀粉样变性的衰减。
Telmisartan, an angiotensin II type 1-receptor blocker (ARBs), has been reported to exert beneficial effects on the central nervous system (CNS). However, the effect of telmisartan on cognitive impairment associated with type 1 diabetes is not well known. Here, we examined the possibility that telmisartan could improve memory function in a type 1 diabetic mouse model, streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice subjected to the Morris Water Maze (MWM) task exhibited a significant decline of spatial learning and memory. Oral administration of telmisartan at two nonhypotensive doses (0.7 or 0.35 mg/kg) significantly improved memory deficits in STZ-induced diabetic mice. Telmisartan treatment markedly reduced Aβ₄₂, APP, BACE1, RAGE, and NF-κB p65 of the hippocampus and cortex, but did not beneficially affect hyperglycemia and hypoinsulinemia in the STZ-induced diabetic mice compared with untreated diabetic mice. Taken together, our findings suggest that telmisartan ameliorates memory deficits in type 1 diabetic mice, at least partly because of attenuation of amyloidosis in the brain.