Departamento de Biociencias Veterinarias, Facultad de Veterinaria, Universidad de la República, Lasplaces 1550, 11600, Montevideo, CP, Uruguay.
Laboratorio de Señalización Celular y Nanobiología, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, 11600, Montevideo, CP, Uruguay.
Exp Brain Res. 2022 Oct;240(10):2687-2699. doi: 10.1007/s00221-022-06446-z. Epub 2022 Aug 19.
Individuals with diabetes mellitus (DM) tend to manifest anxiety and depression, which could be related to changes in the expression of calcium/calmodulin-dependent protein kinase IV (CaMKIV), transcription factor cyclic AMP-responsive element binding protein (CREB), phosphorylated CREB (pCREB) and brain-derived neurotrophic factor (BDNF) in different brain regions. The objective of this study was to determine whether mice with type 1 diabetes (T1DM) induced with streptozotocin show a profile of anxious-type behaviors and alterations in the expression/activity of CaMKIV, CREB, pCREB and BDNF in different regions of the brain (prefrontal cortex, amygdala, hippocampus and hypothalamus) in comparison to non-diabetic mice (NDB). Mice with 3 months of chronic DM showed an anxious-like behavioral profile in two anxiety tests (Open Field and Elevated Plus Maze), when compared to NDB. There were significant differences in the expression of cell signaling proteins: diabetic mice had a lower expression of CaMKIV in the hippocampus, a greater expression of CREB in the amygdala and hypothalamus, as well as a lower pCREB/CREB in hypothalamus than NDB mice (P < 0.05). This is the first study evaluating the expression of CaMKIV in the brain of animals with DM, who presented lower expression of this protein in the hippocampus. In addition, it is the first time that CREB was evaluated in amygdala and hypothalamus of animals with DM, who presented a higher expression. Further research is necessary to determine the possible link between expression of CaMKIV and CREB, and the behavioral profile of anxiety in diabetic animals.
患有糖尿病（DM）的个体往往表现出焦虑和抑郁，这可能与钙/钙调蛋白依赖性蛋白激酶 IV（CaMKIV）、转录因子环磷酸腺苷反应元件结合蛋白（CREB）、磷酸化 CREB（pCREB）和脑源性神经营养因子（BDNF）在不同脑区的表达变化有关。本研究旨在确定链脲佐菌素诱导的 1 型糖尿病（T1DM）小鼠是否表现出焦虑样行为特征，并与非糖尿病（NDB）小鼠相比，在不同脑区（前额叶皮层、杏仁核、海马和下丘脑）中观察到 CaMKIV、CREB、pCREB 和 BDNF 的表达/活性变化。与 NDB 相比，患有 3 个月慢性 DM 的小鼠在两种焦虑测试（旷场和高架十字迷宫）中表现出焦虑样行为特征。细胞信号蛋白的表达存在显著差异：糖尿病小鼠的海马 CaMKIV 表达较低，杏仁核和下丘脑的 CREB 表达较高，而下丘脑的 pCREB/CREB 表达较低（P<0.05）。这是第一项评估 DM 动物大脑中 CaMKIV 表达的研究，该研究发现这种蛋白在海马中的表达较低。此外，这是首次在 DM 动物的杏仁核和下丘脑评估 CREB，发现其表达较高。需要进一步研究以确定 CaMKIV 和 CREB 的表达与糖尿病动物焦虑行为特征之间的可能联系。
