Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China.
Hebei Key Laboratory of Turbidity, Hebei Academy of Chinese Medicine Sciences, Shijiazhuang, Hebei, 050011, China.
Behav Brain Res. 2021 Sep 24;414:113463. doi: 10.1016/j.bbr.2021.113463. Epub 2021 Jul 16.
Brain-derived neurotrophic factor (BDNF) can activate the extracellular regulated protein kinase (ERK)/cAMP response element binding protein (CREB) cascade revealing an important role in antidepressant effects. Here, we studied the neuroprotective effect of baicalin (BA) in mice with chronic unpredictable mild stress (CUMS)-induced via a BDNF/ERK/CREB signaling pathway. Depression was induced via six weeks of CUMS in male ICR mice, and drug therapy was given simultaneously for the last three weeks. Cognitive dysfunctions were then evaluated via sucrose preference test (SPT), open field test (OFT), Morris water maze test (MWM), tail suspension test (TST), and novelty suppressed feeding test (NSF). Western blot and real-time PCR were then used to detect the relative expression of ERK, CREB, p-ERK, and p-CREB. Integrated optical density (IOD) tests of p-ERK and p-CREB were then evaluated via immunofluorescence. The behavior results showed that the cognitive dysfunctions increased in the CUMS group versus the control (CON) group (p < 0.01). There were decreases in fluoxetine (FLU) and BA groups (p < 0.05, p < 0.01). The protein ratios of p-ERK/ERK, p-CREB/CREB and ERK mRNA, and CREB mRNA expression decreased in the CUMS group (p < 0.01) and markedly increased in the FLU and BA groups (p < 0.05, p < 0.01). The IOD value of the p-ERK and p-CREB in the CUMS group was decreased versus the CON group (p < 0.01), and these changes were improved via BA and FLU treatment (p < 0.05, p < 0.01). This study indicated that BA can improve cognitive functions and has antidepressant effects in mice, which may be associated with activation of the BDNF/ERK/CREB signaling pathway in the hippocampus.
脑源性神经营养因子（BDNF）可激活细胞外调节蛋白激酶（ERK）/cAMP 反应元件结合蛋白（CREB）级联反应，从而在抗抑郁作用中发挥重要作用。在这里，我们研究了黄芩素（BA）通过 BDNF/ERK/CREB 信号通路对慢性不可预测轻度应激（CUMS）诱导的小鼠的神经保护作用。雄性 ICR 小鼠通过六周的 CUMS 诱导抑郁，最后三周同时进行药物治疗。然后通过蔗糖偏好测试（SPT）、旷场测试（OFT）、Morris 水迷宫测试（MWM）、悬尾测试（TST）和新异抑制摄食测试（NSF）评估认知功能障碍。然后使用 Western blot 和实时 PCR 检测 ERK、CREB、p-ERK 和 p-CREB 的相对表达。通过免疫荧光法评估 p-ERK 和 p-CREB 的整合光密度（IOD）测试。行为结果表明，与对照（CON）组相比，CUMS 组的认知功能障碍增加（p < 0.01）。氟西汀（FLU）和 BA 组减少（p < 0.05，p < 0.01）。CUMS 组的 p-ERK/ERK、p-CREB/CREB 和 ERK mRNA 比值以及 CREB mRNA 表达降低（p < 0.01），FLU 和 BA 组显著增加（p < 0.05，p < 0.01）。与 CON 组相比，CUMS 组的 p-ERK 和 p-CREB 的 IOD 值降低（p < 0.01），通过 BA 和 FLU 治疗改善了这些变化（p < 0.05，p < 0.01）。这项研究表明，BA 可以改善认知功能，并且在小鼠中具有抗抑郁作用，这可能与海马中 BDNF/ERK/CREB 信号通路的激活有关。
