Department of Neurophysiology and Neuropharmacology, Medical University of Vienna, 1090 Vienna, Austria.
Department of Paediatrics, Division of Neonatology, Pediatric Intensive Care Medicine and Neuropaediatrics, Medical University of Vienna, 1090 Vienna, Austria.
Cells. 2020 Apr 22;9(4):1048. doi: 10.3390/cells9041048.
Maternal immune activation (MIA) during pregnancy impacts offspring neurodevelopmental trajectories and induces lifelong consequences, including emotional and cognitive alterations. Using the polyinosinic:polycytidilic acid (PIC) MIA model we have previously demonstrated enhanced depression-like behavior in adult MIA offspring, which was associated with reduced expression of the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) in the hippocampus. Since VEGF mediates the effects of various antidepressant agents, we here set out to explore whether VEGF administration could rescue the depression-like behavioral deficits in MIA offspring. To test our hypothesis, control and MIA offspring were intracerebroventricularly (i.c.v.) infused with either VEGF or vehicle solution and depression-related behavior was assessed in the sucrose preference test (SPT) and the tail suspension test (TST). As a surrogate of VEGF activity, the phosphorylation of the extracellular signal-regulated kinase (ERK) in hippocampus was quantified. We found that VEGF treatment reduced depression-related behavioral despair in the TST in MIA offspring but had no effect on anhedonia-like behavior in the SPT. While VEGF administration induced the phosphorylation of ERK in the hippocampus of control offspring, this effect was blunted in the MIA offspring. We conclude that VEGF administration, at the dosage tested, beneficially affects some aspects of the depression-like phenotype in the adult MIA offspring, inviting further studies using different dosage regimes to further explore the therapeutic potential of VEGF treatment in MIA-related changes in brain function and behavior.
母体免疫激活 (MIA) 在怀孕期间会影响后代的神经发育轨迹，并导致终生的影响，包括情绪和认知的改变。我们之前使用聚肌胞苷酸（PIC）MIA 模型证明，成年 MIA 后代中出现了更严重的抑郁样行为，这与海马体中血管内皮生长因子 (VEGF) 受体 2 (VEGFR2) 的表达减少有关。由于 VEGF 介导了各种抗抑郁药物的作用，我们在这里探讨了 VEGF 给药是否可以挽救 MIA 后代的抑郁样行为缺陷。为了验证我们的假设，对照组和 MIA 后代通过脑室内 (i.c.v.) 注射 VEGF 或载体溶液，并在蔗糖偏好测试 (SPT) 和悬尾测试 (TST) 中评估与抑郁相关的行为。作为 VEGF 活性的替代物，我们对海马体中细胞外信号调节激酶 (ERK) 的磷酸化进行了定量。我们发现，VEGF 处理可减少 MIA 后代在 TST 中的抑郁相关行为绝望，但对 SPT 中的快感缺失样行为没有影响。虽然 VEGF 给药诱导了对照组后代海马体中 ERK 的磷酸化，但这种作用在 MIA 后代中被削弱了。我们得出结论，在测试的剂量下，VEGF 给药对成年 MIA 后代的抑郁样表型的某些方面有益，这促使我们使用不同的剂量方案进一步探索 VEGF 治疗在 MIA 相关的大脑功能和行为变化中的治疗潜力。
