Department of Pharmacy and Pharmacology, Brazil.
Behav Brain Res. 2010 Jun 26;210(1):38-45. doi: 10.1016/j.bbr.2010.02.001. Epub 2010 Feb 6.
We investigated the effects of chronic administration of vitamin E on nitric oxide (NO)-producing neurons in the brains of streptozotocin (STZ)-induced diabetic rats using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. We further evaluated the effects of diabetes and vitamin E treatment on experimental anxiety and memory processes using the elevated plus maze (EPM) Trial 1/2 protocol. Wistar rats were divided into four groups: normoglycemics (N), normoglycemics treated with vitamin E (NVE), diabetics (D), and diabetics treated with vitamin E (DVE). Diabetes mellitus was induced by a single intraperitoneal injection of STZ (35mg/kg). Vitamin E (100mg/kg) or vehicle was administered orally by gavage (1ml/kg) once each day for 7 weeks. After behavioral testing, the dentate gyrus of the hippocampus (DG), striatum, paraventricular nucleus of the hypothalamus (PVN), supraoptic nucleus (SON), and dorsolateral periaqueductal grey (DLPAG) were analyzed for NADPH-d histochemistry. STZ-induced diabetic rats exhibited decreased locomotor activity and cognitive impairment compared with normoglycemic controls. The number of NADPH-d-positive neurons was increased in the DG, striatum, and DLPAG of diabetic rats. An increase in soma area was detected in all structures analyzed (DG, striatum, PVN, SON, and DLPAG) of STZ-induced diabetic animals. The present study showed that chronic administration of vitamin E ameliorates memory in STZ-induced diabetic rats and revealed that NOS-producing neurons have an increased soma area which can be restored, at least partially, by vitamin E treatment. These results suggest the potential use of vitamin E as an adjuvant therapy for the prevention and treatment of diabetic conditions.
我们使用烟酰胺腺嘌呤二核苷酸磷酸-黄递酶（NADPH-d）组织化学研究了慢性给予维生素 E 对链脲佐菌素（STZ）诱导的糖尿病大鼠大脑中产生一氧化氮（NO）的神经元的影响。我们进一步使用高架十字迷宫（EPM）试验 1/2 方案评估了糖尿病和维生素 E 治疗对实验性焦虑和记忆过程的影响。Wistar 大鼠分为四组：正常血糖组（N）、正常血糖组给予维生素 E 治疗组（NVE）、糖尿病组（D）和糖尿病组给予维生素 E 治疗组（DVE）。糖尿病通过单次腹腔注射 STZ（35mg/kg）诱导。维生素 E（100mg/kg）或载体通过灌胃（1ml/kg）每天口服给药一次，持续 7 周。行为测试后，分析海马齿状回（DG）、纹状体、下丘脑室旁核（PVN）、视上核（SON）和外侧导水管周围灰质（DLPAG）的 NADPH-d 组织化学。与正常血糖对照组相比，STZ 诱导的糖尿病大鼠表现出运动活动减少和认知障碍。糖尿病大鼠 DG、纹状体和 DLPAG 中 NADPH-d 阳性神经元数量增加。在所有分析的结构（DG、纹状体、PVN、SON 和 DLPAG）中均检测到神经元体面积增加。本研究表明，慢性给予维生素 E 可改善 STZ 诱导的糖尿病大鼠的记忆，并表明产生 NOS 的神经元的神经元体面积增加，至少部分可通过维生素 E 治疗得到恢复。这些结果表明，维生素 E 作为预防和治疗糖尿病的辅助治疗具有潜在用途。
