School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China; Foshan Maternal and Child Health Research Institute, Affiliated Hospital of Southern Medical University, Foshan, Guangdong, China.
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China.
Brain Res Bull. 2018 Sep;142:107-115. doi: 10.1016/j.brainresbull.2018.06.019. Epub 2018 Jun 30.
Depression is a heterogeneous disorder, but the exact neuronal mechanisms causing the disease have not yet been discovered.
METHODS/MATERIALS: We have established a chronic unpredictable mild stress (CUMS) mouse model to explore the blood oxygen level-dependent (BOLD) activity in the hippocampus, prefrontal cortex (PFC), and basolateral amygdala (BLA) using amplitude of low-frequency fluctuations (ALFF) in functional magnetic resonance imaging (fMRI). We initially studied the relationship between brain-derived neurotrophic factor (BDNF) expression and BOLD activity using BDNF mice.
We found that CUMS induced depressive-like behaviours and stimulated changes in brain regions expressing a different BDNF level, which was decreased in the hippocampus and PFC but increased in the BLA. In contrast, the BOLD activity was elevated in the hippocampus and PFC but reduced in the BLA after CUMS exposure, indicating that the BDNF level negatively correlated with the BOLD activity in the WT CUMS-exposed mice. Moreover, the depressive-like behaviours and region-specific BOLD activity in BDNF mice were consistent with those in WT CUMS-exposed mice.
We surmised that critical neural circuitry connects the hippocampus, PFC and BLA in mice, which was regulated by BDNF to protect against depression. These findings suggested a potential central role of BDNF expression in functional changes in the brain.
抑郁症是一种异质性疾病，但导致这种疾病的确切神经元机制尚未被发现。
方法/材料：我们建立了慢性不可预测轻度应激（CUMS）小鼠模型，使用功能磁共振成像（fMRI）中的低频波动幅度（ALFF）来探索海马体、前额叶皮层（PFC）和基底外侧杏仁核（BLA）中的血氧水平依赖（BOLD）活动。我们最初使用 BDNF 小鼠研究了脑源性神经营养因子（BDNF）表达与 BOLD 活动之间的关系。
我们发现 CUMS 诱导了抑郁样行为，并刺激了表达不同 BDNF 水平的大脑区域发生变化，海马体和 PFC 中的 BDNF 水平降低，而 BLA 中的 BDNF 水平升高。相反，CUMS 暴露后，海马体和 PFC 中的 BOLD 活性升高，而 BLA 中的 BOLD 活性降低，表明 WT CUMS 暴露小鼠的 BDNF 水平与 BOLD 活性呈负相关。此外，BDNF 小鼠的抑郁样行为和区域特异性 BOLD 活性与 WT CUMS 暴露小鼠一致。
我们推测，小鼠的海马体、PFC 和 BLA 之间存在关键的神经回路，BDNF 通过调节这些回路来预防抑郁。这些发现表明 BDNF 表达在大脑功能变化中可能发挥核心作用。
