Role of vascular endothelial growth factor as a critical neurotrophic factor for the survival and physiology of motoneurons

查看全文 作　　者：Paula [1]M.Calvo;Rosendo [1]G.Hernández;Rosa R.de la [1]Cruz;Angel [1]M.Pastor 机构地区：[1]Departamento de Fisiología,Facultad de Biología,Universidad de Sevilla,Sevilla,Spain 出　　处：《Neural Regeneration Research》索引2023年第18卷第8期,共6页 基　　金：supported by the I+D+i project P20_00529 Consejería de Transformación Económica Industria y Conocimiento,Junta de Andalucía-FEDER;supported by project PGC2018-094654-B-100 and PID2021-124300NB-I00 funded by MCIN/AEI/FEDER“A way of making Europe”;P.M.C.was a scholar of Ministerio de Educación y Ciencia(BES-2016-077912)in Spain and is now a“Margarita Salas”postdoctoral fellow;RGH is a postdoctoral fellow from PAIDI-2019,“Talento Doctores”Junta de Andalucía in Spain,and is now a“Ramón y Cajal”fellow in Spain。 摘　　要：Vascular endothelial growth factor(VEGF)was discovered by its angiogenic activity.However,during evolution,it appeared earlier as a neurotrophic factor required for the development of the nervous system in invertebrates lacking a circulatory system.We aimed at reviewing recent evidence indicating that VEGF has neuroprotective effects in neurons exposed to a variety of insults.Of particular interest is the link established between VEGF and motoneurons,especially after the design of the VEGFδ/δmutant mice.These mice are characterized by low levels of VEGF and develop muscle weakness and motoneuron degeneration resembling amyotrophic lateral sclerosis.The administration of VEGF through several routes to animal models of amyotrophic lateral sclerosis delays motor impairment and motoneuron degeneration and increases life expectancy.There are new recent advances in the role of VEGF in the physiology of motoneurons.Our experimental aims use the extraocular(abducens)motoneurons lesioned by axotomy as a model for studying VEGF actions.Axotomized abducens motoneurons exhibit severe alterations in their discharge activity and a loss of synaptic boutons.The exogenous administration of VEGF to axotomized abducens motoneurons,either from the transected nerve or intraventricularly,fully restores the synaptic and discharge properties of abducens motoneurons,despite being axotomized.In addition,when an anti-VEGF neutralizing antibody is delivered from the muscle to intact,uninjured abducens motoneurons,these cells display alterations in their discharge pattern and a loss of synaptic boutons that resemble the state of axotomy.All these data indicate that VEGF is an essential neurotrophic factor for motoneurons. 关 键 词：abducens nucleus amyotrophic lateral sclerosis cell death extracellular single-unit recordings eye movements NEURODEGENERATION OCULOMOTOR trophic factors