Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria - RS, Brazil, Zip Code: 97105-900, Brazil.
Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria - RS, Brazil, Zip Code: 97105-900, Brazil.
Physiol Behav. 2021 Aug 1;237:113346. doi: 10.1016/j.physbeh.2021.113346. Epub 2021 Feb 3.
Prediabetes is the stage before diabetes in which not all the symptoms or signs required to diagnose diabetes are present, but blood glucose is abnormally high. This study investigates if memory impairment and depressive-like phenotype are accompanied by the hippocampal insulin and BDNF signaling in prediabetic mice. Male adult Swiss mice received streptozotocin (STZ, 200 mg/kg, ip) to induce prediabetes. Control mice were treated with citrate buffer (5 ml/kg, ip). To characterize prediabetes status, metabolic parameters were determined in mice. The behavioral test battery to assess memory consisted of object recognition (ORT), object location (OLT), and Morris water maze (MWM) tests. The mouse depressive-like phenotype was investigated using the forced swimming (FST) and tail suspension (TST) tests. The pIRS-1/Akt/GLUT4 and BDNF/TrkB/CREB protein contents were determined in the hippocampus of mice. Prediabetic mice showed mild hyperglycemia, reduced body weight gain, and an increase in glucose and insulin tolerance tests (AUCs). Prediabetic mice had smaller recognition and location indexes, in the ORT and OLT, than the control group. Prediabetic mice showed hippocampus-dependent spatial memory impairment, in the MWM test, and an increase in immobility time, in the TST and FST, compared to the control group. The molecular findings indicate the downregulation of hippocampal insulin and BDNF signaling in prediabetic mice. In conclusion, memory impairment and depressive-like phenotype were potentially linked to the downregulation of hippocampal pIRS-1/Akt/GLUT4 and BDNF/CREB signaling in prediabetic mice.
糖尿病前期是指尚未达到糖尿病诊断标准但血糖已经异常升高的阶段。本研究旨在探讨糖尿病前期小鼠是否存在海马胰岛素和 BDNF 信号转导异常伴发的记忆障碍和抑郁样表型。雄性成年瑞士小鼠经腹腔注射链脲佐菌素（STZ，200mg/kg）诱导糖尿病前期，对照组小鼠则给予柠檬酸缓冲液（5ml/kg，腹腔注射）。通过检测代谢参数对糖尿病前期状态进行特征分析。采用物体识别（ORT）、物体定位（OLT）和 Morris 水迷宫（MWM）测试评估记忆行为。利用强迫游泳（FST）和悬尾（TST）测试评估小鼠的抑郁样表型。通过 Western blot 检测海马 pIRS-1/Akt/GLUT4 和 BDNF/TrkB/CREB 蛋白含量。糖尿病前期小鼠表现为轻度高血糖、体重增长缓慢以及葡萄糖和胰岛素耐量试验（AUC）增加。与对照组相比，糖尿病前期小鼠在 ORT 和 OLT 中的识别指数和定位指数均减小。与对照组相比，糖尿病前期小鼠在 MWM 测试中表现出海马依赖性空间记忆障碍，在 TST 和 FST 中表现出不动时间增加。分子学研究结果表明，糖尿病前期小鼠的海马胰岛素和 BDNF 信号转导下调。综上，记忆障碍和抑郁样表型可能与糖尿病前期小鼠海马 pIRS-1/Akt/GLUT4 和 BDNF/CREB 信号转导下调有关。
