IGF-II and Insulin Receptors in Neural Stem Cells
IGF-II and Insulin Receptors in Neural Stem Cells
批准号:
8643924
负责人:
STEVEN W LEVISON
金额:
$19.88万
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-09-15 至 2015-08-31
关键词:
1 year oldAdoptionAdultAffectAgeAgingAlternative SplicingAntibodiesBathingBehavioralBindingBirthBloodBlood CirculationBrainBrain DiseasesBrain InjuriesCaenorhabditis elegansCell MaintenanceCellsCerebral VentriclesCerebrospinal FluidColorCommunitiesDataDevelopmentDrosophila genusEmbryonic DevelopmentEpidemiologyFailureFetal GrowthFlow CytometryGoalsGrowthGrowth FactorHippocampus (Brain)HomeostasisHumanHybridsImpaired cognitionInsulinInsulin ReceptorInsulin-Like Growth Factor IInsulin-Like Growth Factor IIInsulin-Like-Growth Factor I ReceptorKnowledgeLabelLeadLearningLifeLongevityMaintenanceMemoryMethodsMolecularMusMutant Strains MiceNeurogliaNeuronsNeurosciencesOrganParahippocampal GyrusPhysiologicalPopulationPositioning AttributeProcessProductionProtein IsoformsPublishingRNA SplicingReceptor SignalingRoleScientific Advances and AccomplishmentsSensorySignal TransductionSmell PerceptionStem cellsStromal CellsStructure of choroid plexusSystemTestingThymidineTissuesVariantactivating transcription factoradult stem cellage relatedaging brainanalogbehavioral deficiencycognitive functiondentate gyrusfetalinjuredinsightinsulin signalinginterestmouse modelmutantnerve stem cellneurogenesisnovelnovel therapeuticsolfactory bulbpostnatalprimitive cellprogenitorpublic health relevancepupreceptorreconstitutionrepairedresearch studyself-renewalstem cell nichestem cell therapystemness
中文摘要
神经前体一直是发育生物学家的兴趣所在。这些细胞具有
最近引起了更广泛的神经科学界的兴趣,因为他们
参与嗅觉,学习和记忆,认知能力随着年龄的增长而下降,
取代因脑损伤或疾病而死亡的神经元或神经胶质细胞。的
重要的细胞是神经干细胞(NSC)。这些细胞自然存在于
在特定的壁龛中,它们接收到维持它们在一个
原始状态迄今为止,IGF-II是干细胞的必要成分的可能性
由于IGF-II被认为是一种胎儿生长,
因子然而,IGF-II在脉络丛内高水平表达,这产生了
神经干细胞容易接近的脑脊液,因为它们直接延伸了一个过程
注入脑室内的脑脊液。而IGF-II和IGF-I都激活
IGF-1型受体(IGF-1 R),IGF-II也与胰岛素的剪接变体同种型结合
胰岛素样生长因子受体(IR-A)支持IGF-II与IGF-I的不同作用。这个问题的总体假设
IGF-II对于NSC的自我更新、维持和发展至关重要,
胰岛素受体。我们的总体假设将使用诱导型Cre驱动系进行测试,
实现IGF-II或胰岛素受体的时间离散缺失。将进行研究
在分子、细胞和行为层面上。确定IGF-II是维持NSC所必需的
将是一个重大的科学进步此外,确定哪个信令
受体和下游转录因子被这个信号激活,
深入了解新的策略来放大这些重要的细胞,以促进大脑生长,
在整个生命周期中的细胞替换,并增强患病或受损细胞的细胞替换
个脑袋IGF-II也在其他有成体干细胞的器官中表达,但IGF-II在成体干细胞中起作用。
IGF-II在成体干细胞维持中尚未在哺乳动物组织中探索。因此,我们认为,
在完成了所提议的实验之后,我们将处于独特的地位,可以提交R 01
调查这些重要而及时的问题。
英文摘要
Neural precursors have long been of interest to developmental biologists. These cells have
recently gained the interest of the broader neuroscience community because of their
involvement in olfaction, learning and memory, cognitive decline with aging and their potential to
replace neurons or glial cells that have died as a consequence of brain injury or disease. The
cells that are of significant interest are the neural stem cells (NSCs). These cells naturally reside
within specific niches where they receive signals that are necessary to maintain them in a
primitive state. To date, the possibility that IGF-II is a necessary component of the stem cell
niche has not been considered largely because IGF-II has been regarded as a fetal growth
factor. However, IGF-II is expressed at high levels within the choroid plexus, which produces the
cerebrospinal fluid that is readily accessible to the NSCs because they extend a process directly
into the ventricle that is bathed by cerebrospinal fluid. Whereas both IGF-II and IGF-I activate
the IGF type 1 receptor (IGF-1R), IGF-II also binds to a splice variant isoform of the insulin
receptor (IR-A) supporting distinct roles for IGF-II versus IGF-I. The overall hypothesis of this
proposal is that IGF-II is essential for NSC self-renewal, maintenance and growth through
the insulin receptor. Our overall hypothesis will be tested using inducible Cre driver lines to
achieve both temporal discrete deletion of IGF-II or insulin receptors. Studies will be performed
at the molecular, cellular and behavioral levels. Identifying IGF-II as necessary to sustain NSCs
as primitive cells will be a significant scientific advance. Moreover, establishing which signaling
receptor and downstream transcription factors are activated by this signal might well provide
insights into new strategies to amplify these important cells to promote brain growth, maintain
cell replacement across the lifespan and enhance cell replacement in the diseased or damaged
brain. IGF-II is also expressed in other organs where there are adult stem cells, yet a role for
IGF-II in adult stem cell maintenance has not been explored in mammalian tissues. Therefore,
upon completing the proposed experiments we will be uniquely positioned to submit an R01
application to investigate these important and timely issues.
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会议论文
Intranasal LIF to improve neurological recovery from perinatal hypoxia-ischema
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批准号:10350660
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项目类别:
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资助金额:$33.95万
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财政年份:2020
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负责人:STEVEN W LEVISON
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依托单位:
Intranasal LIF to improve neurological recovery from perinatal hypoxia-ischema
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批准号:9980145
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项目类别:
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资助金额:$38.15万
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财政年份:2020
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负责人:STEVEN W LEVISON
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依托单位:
Intranasal LIF to improve neurological recovery from perinatal hypoxia-ischema
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批准号:10555280
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项目类别:
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资助金额:$33.95万
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财政年份:2020
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负责人:STEVEN W LEVISON
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依托单位:
IGF-II and Insulin Receptors in Neural Stem Cells
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批准号:8734489
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项目类别:
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资助金额:$23.61万
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财政年份:2013
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负责人:STEVEN W LEVISON
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依托单位:
American Society for Neurochemistry 44th Annual Meeting
-
批准号:8529173
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项目类别:
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资助金额:$2.7万
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财政年份:2013
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负责人:STEVEN W LEVISON
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依托单位:
American Society for Neurochemistry 43rd Annual Meeting
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批准号:8319005
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项目类别:
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资助金额:$2.5万
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财政年份:2012
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负责人:STEVEN W LEVISON
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依托单位:
Glial Dysgenesis in the Injured Developing Brain
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批准号:8066317
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项目类别:
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资助金额:$25.63万
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财政年份:2010
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负责人:STEVEN W LEVISON
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依托单位:
Glial Dysgenesis in the Injured Developing Brain
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批准号:7889970
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项目类别:
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资助金额:$30.4万
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财政年份:2010
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负责人:STEVEN W LEVISON
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依托单位:
Glial Dysgenesis in the Injured Developing Brain
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批准号:8717070
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项目类别:
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资助金额:$39.08万
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财政年份:2010
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负责人:STEVEN W LEVISON
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依托单位:
Glial Dysgenesis in the Injured Developing Brain
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批准号:8443451
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项目类别:
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资助金额:$14.82万
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财政年份:2010
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负责人:STEVEN W LEVISON
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依托单位:
Glial Dysgenesis in the Injured Developing Brain
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批准号:8442313
-
项目类别:
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资助金额:$0.0万
-
财政年份:2010
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负责人:STEVEN W LEVISON
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依托单位:
Glial Dysgenesis in the Injured Developing Brain
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批准号:8241073
-
项目类别:
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资助金额:$25.8万
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财政年份:2010
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负责人:STEVEN W LEVISON
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依托单位:
CELLULAR DIFFERENTIATION
-
批准号:6318364
-
项目类别:
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资助金额:$15.82万
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财政年份:2000
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负责人:STEVEN W LEVISON
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依托单位:
CEREBRAL DYSGENESIS AFTER PERINATAL HYPOXIA/ISCHEMIA
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批准号:2842857
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项目类别:
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资助金额:$16.18万
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财政年份:1999
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负责人:STEVEN W LEVISON
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依托单位:
Neural Stem Cell Responses to Perinatal Brain Damage
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批准号:7228183
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财政年份:1999
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负责人:STEVEN W LEVISON
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CEREBRAL DYSGENESIS AFTER PERINATAL HYPOXIA/ISCHEMIA
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负责人:STEVEN W LEVISON
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财政年份:1999
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负责人:STEVEN W LEVISON
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依托单位:
Neural Stem Cell Responses to Perinatal Brain Damage
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批准号:6894249
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财政年份:1999
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负责人:STEVEN W LEVISON
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CEREBRAL DYSGENESIS AFTER PERINATAL HYPOXIA/ISCHEMIA
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批准号:6528562
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资助金额:$15.99万
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财政年份:1999
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负责人:STEVEN W LEVISON
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依托单位:
Neural Stem Cell Responses to Perinatal Brain Damage
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批准号:7058737
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资助金额:$30.37万
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财政年份:1999
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依托单位:
海外基金