Abstract
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.
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Acknowledgements
This study was partially supported by the National Council of Science and Technology of Mexico (CONACYT) through Grant No. 177594 given to CBZ, GGC and MEUG as members of the same research group and through Scholarship No. 510027 given to JLCC. In addition, regular financial support given to MEUG as a researcher of CUCBA-University of Guadalajara during the last 3 years was applied in this study.
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Castañeda-Cabral, J.L., Beas-Zarate, C., Gudiño-Cabrera, G. et al. Glutamate Neonatal Excitotoxicity Modifies VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 Protein Expression Profiles During Postnatal Development of the Cerebral Cortex and Hippocampus of Male Rats. J Mol Neurosci 63, 17–27 (2017). https://doi.org/10.1007/s12031-017-0952-7
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DOI: https://doi.org/10.1007/s12031-017-0952-7