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 invertebrat...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.展开更多
The consequences of neonatal white matter injury are devastating and represent a major societal problem as currently there is no cure.Prematurity,low weight birth and maternal pre-natal infection are the most frequent...The consequences of neonatal white matter injury are devastating and represent a major societal problem as currently there is no cure.Prematurity,low weight birth and maternal pre-natal infection are the most frequent causes of acquired myelin deficiency in the human neonate leading to cerebral palsy and cognitive impairment.In the developing brain,oligodendrocyte(OL)maturation occurs perinatally,and immature OLs are particularly vulnerable.Cell replacement therapy is often considered a viable option to replace progenitors that die due to glutamate excitotoxicity.We previously reported directed specification and mobilization of endogenous committed and uncommitted neural progenitors by the combination of transferrin and insulin growth factor 1(TSC1).Here,considering cell replacement and integration as therapeutic goals,we examined if OL progenitors(OLPs)grafted into the brain parenchyma of mice that were subjected to an excitotoxic insult could rescue white matter injury.For that purpose,we used a well-established model of glutamate excitotoxic injury.Four-day-old mice received a single intraparenchymal injection of the glutamate receptor agonist N-methyl-D-aspartate alone or in conjunction with TSC1 in the presence or absence of OLPs grafted into the brain parenchyma.Energetics and expression of stress proteins and OL developmental specific markers were examined.A comparison of the proteomic profile per treatment was also ascertained.We found that OLPs did not survive in the excitotoxic environment when grafted alone.In contrast,when combined with TSC1,survival and integration of grafted OLPs was observed.Further,energy metabolism in OLPs was significantly increased by N-methyl-D-aspartate and modulated by TSC1.The proteomic profile after the various treatments showed elevated ubiquitination and stress/heat shock protein 90 in response to N-methyl-D-aspartate.These changes were reversed in the presence of TSC1 and ubiquitination was decreased.The results obtained in this pre-clinical study indicate that the use of a combinatorial intervention including both trophic support and healthy OLPs constitutes a promising approach for long-term survival and successful graft integration.We established optimal conditioning of the host brain environment to promote long-term survival and integration of grafted OLPs into an inflamed neonate host brain.Experimental procedures were performed under the United States Public Health Service Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care Committee at(UCLA)(ARC#1992-034-61)on July 1,2010.展开更多
The gastrointestinal tract(GIT) is a complex system, which changes in response to requirements of the body. GIT represents a barrier to the external environment. To achieve this, epithelial cells must renew rapidly. T...The gastrointestinal tract(GIT) is a complex system, which changes in response to requirements of the body. GIT represents a barrier to the external environment. To achieve this, epithelial cells must renew rapidly. This renewal of epithelial cells starts in the fetal life under the influence of many GIT peptides by swallowing amniotic fluid(AF). Development and maturation of GIT is a very complex cascade that begins long before birth and continues during infancy and childhood by breastfeeding. Many factors like genetic preprogramming, local and systemic endocrine secretions and many trophic factors(TF) from swallowed AF contribute and modulate the development and growth of the GIT. GIT morphogenesis, differentiation and functional development depend on the activity of various TF in the AF. This manuscript will review the role of AF borne TF in the development of GIT.展开更多
The carotid body (CB) is a small neural crest-derived organ that registers oxygen and glucose levels in blood and regulates ventilation. The most abundant cell type in the CB glomeruli is glomus or type I cells, which...The carotid body (CB) is a small neural crest-derived organ that registers oxygen and glucose levels in blood and regulates ventilation. The most abundant cell type in the CB glomeruli is glomus or type I cells, which is enveloped by processes of sustentacular or type II cells. Growth and neurotrophic factors have been established as signaling molecules played an important role in the development of the CB. To gain insight whether these signaling molecules are present in the adult rat CB, we examined the expression and cellular localization of some neurotrophic factors and their corresponding receptors in this organ by immunohistochemistry. The results showed the presence of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) as well as p75NTR, tyrosine kinase A receptor (TrkA), tyrosine kinase B receptor (TrkB) and GDNF family receptor alpha1 (GFRα1) in the adult CB. At the light-microscopical level, the immunoreactivity for NGF and both its low-affinity (p75) and high-affinity (TrkA) receptors was detected in the majority of glomus cells and also in a subset of sustentacular cells. BDNF and its receptors, p75 and TrkB, were observed in the glomus cells, too. Remarkably, the immunohistochemical analysis revealed that the neuron-like glomus cells, but not the glial-like sustentacular cells, expressed GDNF and GFRα1. Taken together with prior results, it can be inferred that neurotrophins may be involved in the CB cell differentiation and survival in adulthood, and may exert a potent glomic protective action as well. It is also presumable that GDNF production by glomus cells plays a pivotal role in permitting long-term viability of CB grafts, which permits their potential applicability in cell therapy as a promising tool in neurodegenerative disorders.展开更多
The effect of the extract from caudate-putamen nucleus of newborn rats(CPe)on thedopaminergic(DA)neurons has been studied.An MTT colorimetric microassay measuring optical densitiesfor the growth of DA neuron cultures ...The effect of the extract from caudate-putamen nucleus of newborn rats(CPe)on thedopaminergic(DA)neurons has been studied.An MTT colorimetric microassay measuring optical densitiesfor the growth of DA neuron cultures reveals a significant increase in growth for cultures with CPe as com-pared to those without CPe(p【0.05).Rhodamine retrograde-prelabelled DA neurons were cultured on aPhastgel containing all the electrophoretically separated protein bands from CPe,and able to fish out from ittheir own trophic factor,a 12.5-kD protein band.The survived neurons at the 12.5-kD protein band wereimmunostained positive with anti-dopamine antibody.Co-culturing the 12.5 kD-containing gel strip with ex-plants from substantia nigra at a close distance for a week revealed anti-dopamine immunopositive neuritesoutgrowing from the explants only towards the 12.5-kD gel strip.These results indicate that a 12.5-kD pro-tein from the CPe is capable of maintaining the survival of DA neurons of the substantia nigra and promotingtheir neurite outgrowth.展开更多
[Objective] The aim was to study the relationship between chlorophyll-a and environmental impact factors in deep reservoir in Karst Areas.[Method] Taking Aha Reservoir for example,the changes of chlorophyll-a content ...[Objective] The aim was to study the relationship between chlorophyll-a and environmental impact factors in deep reservoir in Karst Areas.[Method] Taking Aha Reservoir for example,the changes of chlorophyll-a content and its relationship with environmental impact factors were researched,and the water quality of Aha Reservoir was assessed by means of modified Carlson trophic state index.[Result] Chlorophyll-a content in Aha Reservoir was higher in March,April,May and September and lower from June to August,and there was obvious seasonal variation,namely its variation trend was spring>summer>autumn>winter.In addition,chlorophyll-a content showed extremely significant correlation with transparency and dissolved oxygen (P<0.01) and significant correlation with ammonia nitrogen (P<0.05).Meanwhile,trophic state index was higher in whole year in Aha Reservoir which was in moderate trophic state in August,October and November and eutrophic state in other months.[Conclusion] The study could provide scientific reference for discussing the mechanism of lake eutrophication.展开更多
基金supported by the I+D+i project P20_00529 Consejería de Transformación Económica Industria y Conocimiento,Junta de Andalucía-FEDERsupported by project PGC2018-094654-B-100 and PID2021-124300NB-I00 funded by MCIN/AEI/FEDER“A way of making Europe”+1 种基金P.M.C.was a scholar of Ministerio de Educación y Ciencia(BES-2016-077912)in Spain and is now a“Margarita Salas”postdoctoral fellowRGH is a postdoctoral fellow from PAIDI-2019,“Talento Doctores”Junta de Andalucía in Spain,and is now a“Ramón y Cajal”fellow in Spain。
文摘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.
基金The Cell Culture Core supported by grant No.PP1498:Neural Cell Culture Core and NIH grant No.04612 Intellectual&Developmental Disabilities.The Cell,Circuits and Systems Analysis Core is supported by NICHD award No.U54HD087101-03
文摘The consequences of neonatal white matter injury are devastating and represent a major societal problem as currently there is no cure.Prematurity,low weight birth and maternal pre-natal infection are the most frequent causes of acquired myelin deficiency in the human neonate leading to cerebral palsy and cognitive impairment.In the developing brain,oligodendrocyte(OL)maturation occurs perinatally,and immature OLs are particularly vulnerable.Cell replacement therapy is often considered a viable option to replace progenitors that die due to glutamate excitotoxicity.We previously reported directed specification and mobilization of endogenous committed and uncommitted neural progenitors by the combination of transferrin and insulin growth factor 1(TSC1).Here,considering cell replacement and integration as therapeutic goals,we examined if OL progenitors(OLPs)grafted into the brain parenchyma of mice that were subjected to an excitotoxic insult could rescue white matter injury.For that purpose,we used a well-established model of glutamate excitotoxic injury.Four-day-old mice received a single intraparenchymal injection of the glutamate receptor agonist N-methyl-D-aspartate alone or in conjunction with TSC1 in the presence or absence of OLPs grafted into the brain parenchyma.Energetics and expression of stress proteins and OL developmental specific markers were examined.A comparison of the proteomic profile per treatment was also ascertained.We found that OLPs did not survive in the excitotoxic environment when grafted alone.In contrast,when combined with TSC1,survival and integration of grafted OLPs was observed.Further,energy metabolism in OLPs was significantly increased by N-methyl-D-aspartate and modulated by TSC1.The proteomic profile after the various treatments showed elevated ubiquitination and stress/heat shock protein 90 in response to N-methyl-D-aspartate.These changes were reversed in the presence of TSC1 and ubiquitination was decreased.The results obtained in this pre-clinical study indicate that the use of a combinatorial intervention including both trophic support and healthy OLPs constitutes a promising approach for long-term survival and successful graft integration.We established optimal conditioning of the host brain environment to promote long-term survival and integration of grafted OLPs into an inflamed neonate host brain.Experimental procedures were performed under the United States Public Health Service Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care Committee at(UCLA)(ARC#1992-034-61)on July 1,2010.
文摘The gastrointestinal tract(GIT) is a complex system, which changes in response to requirements of the body. GIT represents a barrier to the external environment. To achieve this, epithelial cells must renew rapidly. This renewal of epithelial cells starts in the fetal life under the influence of many GIT peptides by swallowing amniotic fluid(AF). Development and maturation of GIT is a very complex cascade that begins long before birth and continues during infancy and childhood by breastfeeding. Many factors like genetic preprogramming, local and systemic endocrine secretions and many trophic factors(TF) from swallowed AF contribute and modulate the development and growth of the GIT. GIT morphogenesis, differentiation and functional development depend on the activity of various TF in the AF. This manuscript will review the role of AF borne TF in the development of GIT.
文摘The carotid body (CB) is a small neural crest-derived organ that registers oxygen and glucose levels in blood and regulates ventilation. The most abundant cell type in the CB glomeruli is glomus or type I cells, which is enveloped by processes of sustentacular or type II cells. Growth and neurotrophic factors have been established as signaling molecules played an important role in the development of the CB. To gain insight whether these signaling molecules are present in the adult rat CB, we examined the expression and cellular localization of some neurotrophic factors and their corresponding receptors in this organ by immunohistochemistry. The results showed the presence of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) as well as p75NTR, tyrosine kinase A receptor (TrkA), tyrosine kinase B receptor (TrkB) and GDNF family receptor alpha1 (GFRα1) in the adult CB. At the light-microscopical level, the immunoreactivity for NGF and both its low-affinity (p75) and high-affinity (TrkA) receptors was detected in the majority of glomus cells and also in a subset of sustentacular cells. BDNF and its receptors, p75 and TrkB, were observed in the glomus cells, too. Remarkably, the immunohistochemical analysis revealed that the neuron-like glomus cells, but not the glial-like sustentacular cells, expressed GDNF and GFRα1. Taken together with prior results, it can be inferred that neurotrophins may be involved in the CB cell differentiation and survival in adulthood, and may exert a potent glomic protective action as well. It is also presumable that GDNF production by glomus cells plays a pivotal role in permitting long-term viability of CB grafts, which permits their potential applicability in cell therapy as a promising tool in neurodegenerative disorders.
基金the University of Hong Kong and the Growth Factor
文摘The effect of the extract from caudate-putamen nucleus of newborn rats(CPe)on thedopaminergic(DA)neurons has been studied.An MTT colorimetric microassay measuring optical densitiesfor the growth of DA neuron cultures reveals a significant increase in growth for cultures with CPe as com-pared to those without CPe(p【0.05).Rhodamine retrograde-prelabelled DA neurons were cultured on aPhastgel containing all the electrophoretically separated protein bands from CPe,and able to fish out from ittheir own trophic factor,a 12.5-kD protein band.The survived neurons at the 12.5-kD protein band wereimmunostained positive with anti-dopamine antibody.Co-culturing the 12.5 kD-containing gel strip with ex-plants from substantia nigra at a close distance for a week revealed anti-dopamine immunopositive neuritesoutgrowing from the explants only towards the 12.5-kD gel strip.These results indicate that a 12.5-kD pro-tein from the CPe is capable of maintaining the survival of DA neurons of the substantia nigra and promotingtheir neurite outgrowth.
基金Supported by Social Development Project of Guiyang City (2009304,2010503)
文摘[Objective] The aim was to study the relationship between chlorophyll-a and environmental impact factors in deep reservoir in Karst Areas.[Method] Taking Aha Reservoir for example,the changes of chlorophyll-a content and its relationship with environmental impact factors were researched,and the water quality of Aha Reservoir was assessed by means of modified Carlson trophic state index.[Result] Chlorophyll-a content in Aha Reservoir was higher in March,April,May and September and lower from June to August,and there was obvious seasonal variation,namely its variation trend was spring>summer>autumn>winter.In addition,chlorophyll-a content showed extremely significant correlation with transparency and dissolved oxygen (P<0.01) and significant correlation with ammonia nitrogen (P<0.05).Meanwhile,trophic state index was higher in whole year in Aha Reservoir which was in moderate trophic state in August,October and November and eutrophic state in other months.[Conclusion] The study could provide scientific reference for discussing the mechanism of lake eutrophication.
