Vascular endothelial growth factor (VEGF, also known as VEGF-A) is a pleiotropic factor which is expressed by neurons, astrocytes and perivascular macrophages, as well as endothelial cells, in the brain. Recently, VEGF signaling has been implicated in learning and memory, and several clinical and preclinical studies demonstrate that VEGF inhibitors induce cognitive impairment. However, the role of endogenous neuronal VEGF signaling in recognition memory remains unclear. Recently, we have developed mice with forebrain excitatory neuron-specific deletion of VEGF or its receptor, fetal liver kinase 1 (Flk-1) by crossing Camk2a-Cre mice with Vegfaflox/flox and Flk-1flox/flox mice, respectively. Using these conditional knockout mice, the present study addressed the influence of forebrain excitatory neuron-specific deletion of VEGF or Flk-1 on recognition memory in the novel object recognition test. The results show that both short-term (2 h) and long-term (24 h) recognition memory are impaired by neuron-specific deletion of either Flk-1 or VEGF. These findings indicate the physiological importance of endogenous neuronal VEGF-Flk-1 signaling in recognition memory. In addition, the current results also suggest that the impairment of neuronal VEGF-Flk-1 signaling can be a cause of anti-VEGF chemotherapy-induced cognitive impairment.

中文翻译：

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VEGF 或其受体 Flk-1 的神经元特异性缺失损害识别记忆

血管内皮生长因子（VEGF，也称为 VEGF-A）是一种多效性因子，由大脑中的神经元、星形胶质细胞和血管周围巨噬细胞以及内皮细胞表达。最近，VEGF 信号传导与学习和记忆有关，并且一些临床和临床前研究表明 VEGF 抑制剂会诱发认知障碍。然而，内源性神经元 VEGF 信号在识别记忆中的作用仍不清楚。最近，我们通过将 Camk2a-Cre 小鼠分别与 Vegfaflox/flox 和 Flk-1flox/flox 小鼠杂交，开发了具有前脑兴奋性神经元特异性缺失 VEGF 或其受体胎肝激酶 1 (Flk-1) 的小鼠。使用这些条件敲除小鼠，本研究解决了前脑兴奋性神经元特异性缺失 VEGF 或 Flk-1 对新物体识别测试中识别记忆的影响。结果表明，Flk-1 或 VEGF 的神经元特异性缺失会损害短期（2 小时）和长期（24 小时）识别记忆。这些发现表明内源性神经元 VEGF-Flk-1 信号在识别记忆中的生理重要性。此外，目前的结果还表明，神经元 VEGF-Flk-1 信号传导受损可能是抗 VEGF 化疗引起的认知障碍的原因。这些发现表明内源性神经元 VEGF-Flk-1 信号在识别记忆中的生理重要性。此外，目前的结果还表明，神经元 VEGF-Flk-1 信号传导受损可能是抗 VEGF 化疗引起的认知障碍的原因。这些发现表明内源性神经元 VEGF-Flk-1 信号在识别记忆中的生理重要性。此外，目前的结果还表明，神经元 VEGF-Flk-1 信号传导受损可能是抗 VEGF 化疗引起的认知障碍的原因。