Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias (CUCBA), Universidad de Guadalajara, Zapopan, Jalisco, Mexico.
Laboratorio de Regeneración y Desarrollo Neural, Departamento de Biología Celular y Molecular, CUCBA, Universidad de Guadalajara, Km 15.5 Carretera a Nogales, Camino Ing. Ramón Padilla Sánchez Km 2, 45221, Zapopan, Jalisco, Mexico.
J Mol Neurosci. 2017 Sep;63(1):17-27. doi: 10.1007/s12031-017-0952-7. Epub 2017 Jul 29.
Vascular endothelial growth factor (VEGF) exerts both neuroprotective and proinflammatory effects in the brain, depending on the VEGF (A-E) and VEGF receptor (VEGFR1-3) types involved. Neonatal monosodium glutamate (MSG) treatment triggers an excitotoxic degenerative process associated with several neuropathological conditions, and VEGF messenger RNA (mRNA) expression is increased at postnatal day (PD) 14 in rat hippocampus (Hp) following the treatment. The aim of this work was to establish the changes in immunoreactivity to VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 proteins induced by neonatal MSG treatment (4 g/kg, subcutaneous, at PD1, 3, 5 and 7) in the cerebral motor cortex (CMC) and Hp. Samples collected from PD2 to PD60 from control and MSG-treated male Wistar rats were assessed by western blotting for each protein. Considering that immunoreactivity measured by western blotting is related to the protein expression level, we found that each protein in each cerebral region has a specific expression profile throughout the studied ages, and all profiles were differentially modified by MSG. Specifically, neonatal MSG treatment significantly increased the immunoreactivity to the following: (1) VEGF-A at PD8-PD10 in the CMC and at PD6-PD8 in the Hp; (2) VEGF-B at PD2, PD6 and PD10 in the CMC and at PD8-PD9 in the Hp; and (3) VEGFR-2 at PD6-PD8 in the CMC and at PD21-PD60 in the Hp. Also, MSG significantly reduced the immunoreactivity to the following: (1) VEGF-B at PD8-PD9 and PD45-PD60 in the CMC; and (2) VEGFR-1 at PD4-PD6 and PD14-PD21 in the CMC and at PD4, PD9-PD10 and PD60 in the Hp. Our results indicate that VEGF-mediated signalling is involved in the excitotoxic process triggered by neonatal MSG treatment and should be further characterized.
血管内皮生长因子 (VEGF) 在大脑中发挥神经保护和促炎作用，具体取决于所涉及的 VEGF（A-E）和 VEGF 受体（VEGFR1-3）类型。新生大鼠单谷氨酸钠 (MSG) 处理引发兴奋性毒性退行性过程，与多种神经病理学状况相关，并且在处理后第 14 天，大鼠海马 (Hp) 中的 VEGF 信使 RNA (mRNA) 表达增加。本工作的目的是确定新生大鼠 MSG 处理 (4 g/kg，皮下，PD1、3、5 和 7 时) 后 VEGF-A、VEGF-B、VEGFR-1 和 VEGFR-2 蛋白的免疫反应性变化在大脑运动皮层 (CMC) 和 Hp 中。从对照和 MSG 处理的雄性 Wistar 大鼠的 PD2 至 PD60 收集样本，通过 Western blot 对每种蛋白质进行评估。考虑到 Western blot 测量的免疫反应性与蛋白质表达水平相关，我们发现每个大脑区域的每种蛋白质在整个研究年龄期间都有特定的表达谱，并且所有谱都被 MSG 不同程度地改变。具体而言，新生大鼠 MSG 处理显著增加了以下方面的 VEGF-A 免疫反应性：(1) CMC 中的 PD8-PD10 和 Hp 中的 PD6-PD8；(2) CMC 中的 PD2、PD6 和 PD10 和 Hp 中的 PD8-PD9；以及 (3) CMC 中的 PD6-PD8 和 Hp 中的 PD21-PD60 处的 VEGFR-2。此外，MSG 还显著降低了以下方面的 VEGF-B 免疫反应性：(1) CMC 中的 PD8-PD9 和 PD45-PD60；以及 (2) CMC 中的 PD4-PD6 和 PD14-PD21 以及 Hp 中的 PD4、PD9-PD10 和 PD60。我们的结果表明，VEGF 介导的信号转导参与了新生大鼠 MSG 处理引发的兴奋性毒性过程，应进一步表征。
