Olfactory ensheathing cells and microglia contributions to axon removal in the olfactory system.
嗅觉鞘细胞和小胶质细胞对嗅觉系统中轴突去除的贡献。
基本信息
- 批准号:10046940
- 负责人:
- 金额:$ 42.32万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAddressAdultAlzheimer&aposs DiseaseAnti-Inflammatory AgentsAttentionAxonCD11b AntigensCell AdhesionCellsChemicalsChronicDataDevelopmentDiseaseEventExcisionFamilyGeneticGoalsHistologyHumanHyperthyroidismITGAM geneImmune responseImmunohistochemistryInfiltrationInflammationInflammatoryInflammatory ResponseInjectionsInjuryLamina PropriaLeadLeukocytesLifeLightMethimazoleMicrogliaModelingMononuclearMorphologyMusNasal cavityNatural regenerationNeuraxisNeurodegenerative DisordersNeurogliaNeuronsOlfactory EpitheliumOlfactory NerveOlfactory PathwaysParkinson DiseasePeripheral Nervous SystemPhagocytesPharmaceutical PreparationsPharmacologyPhenotypePlayProcessRoleSchizophreniaSignal PathwaySignal TransductionSignaling MoleculeSmell PerceptionSpinal cord injurySwellingTLR2 geneTestingTherapeuticTherapeutic UsesThinnessTimeTissuesToll-like receptorsTransgenic MiceWestern Blottingaxon growthaxon regenerationcribriform platecytokinedesignin vivointerestmouse modelnervous system disorderneuroinflammationnovelolfactory bulbolfactory neurogenesisolfactory sensory neuronspreventprotective effectreceptorregenerativeresponse to injuryside effectstem cells
项目摘要
Neurogenesis of olfactory sensory neurons is an ongoing process that starts early in
development, continues in adults, and requires that newly generated axons successfully
navigate through the lamina propria, cross the cribriform plate and enter the central nervous
system. At the same time axonal debris from the neurons that die needs to be removed. The
goal of this proposal is by studying the regenerative capacity of the olfactory epithelium to
understand what are the interactions between olfactory sensory neuron axonal debris, olfactory
ensheathing glia, and microglia during regeneration. Despite the interest in the regeneration
process of these neurons for its potential therapeutic use, the most fundamental features of
injury-related axon growth remain unknown. The same can be said about the olfactory
ensheathing glia that allows this axonal outgrowth. An important event to allow the growing of
new axons is the removal of the old ones after the cell body of the olfactory sensory neuron
died. This is done without any signs of infiltration of microglia in the olfactory nerve layer of the
olfactory bulb. We will begin addressing these questions by using a chemical ablation approach
together with our recently developed genetic fate mapping strategy. With this transgenic mouse,
axons can be tracked with extraordinary precision. Injury to the olfactory epithelium will be done
by a single injection of methimazole. Methimazole is a drug commonly used to treat
hyperthyroidism in humans with side effects that include temporal loss of the sense of smell. In
mice, methimazole induces loss of the olfactory epithelium leaving only stem cells that
regenerate the lost neurons. First, we will compare the ability of ensheathing glial cells versus
mononuclear phagocytes to engulf degenerating axons. Because our preliminary data shows no
increase in the infiltration of mononuclear phagocytes, but changes in their morphology were
observed, in the second part of this proposal we will analyze the differentiation of these
phagocytes. Finally, we will look into the signaling molecules that differentiate mononuclear
phagocytes without producing an inflammatory response. The results obtained with this
proposal will prove to be critical in understanding the regeneration process and will be of
general interest to understand how a response to an injury in the central nervous system can
proceed with a minimal inflammatory response.
嗅觉感觉神经元的神经发生是一个持续的过程,
发育,在成年人中继续,并要求新产生的轴突成功地
穿过固有层,穿过筛板,进入中枢神经
系统与此同时,死亡神经元的轴突碎片需要被清除。的
这项建议的目的是通过研究嗅上皮的再生能力,
了解嗅觉感觉神经元轴突碎片,嗅觉神经元和嗅觉神经元之间的相互作用。
成鞘胶质细胞和再生过程中的小胶质细胞。尽管对重建的兴趣
这些神经元的过程,其潜在的治疗用途,最基本的特点,
损伤相关轴突生长仍然未知。嗅觉也是如此
使轴突生长的神经胶质鞘。一个重要的事件,让成长的
新的轴突是在嗅觉感觉神经元的细胞体之后去除旧的轴突
死了这是在没有任何迹象表明小胶质细胞浸润的嗅觉神经层的
嗅球我们将开始通过使用化学消融方法来解决这些问题
再加上我们最近开发的基因定位策略对于这种转基因小鼠,
轴突可以被非常精确地追踪。对嗅上皮的损伤
一次注射甲巯咪唑甲巯咪唑是一种常用于治疗
甲状腺机能亢进症的副作用,包括嗅觉暂时丧失。在
在小鼠中,甲巯咪唑诱导嗅觉上皮的丧失,只留下干细胞,
再生失去的神经元。首先,我们将比较成鞘神经胶质细胞与
单核吞噬细胞吞噬退化的轴突。因为我们的初步数据显示
单核吞噬细胞的浸润增加,但其形态学的变化,
观察到,在本提案的第二部分,我们将分析这些差异
吞噬细胞最后,我们将研究分化单核细胞的信号分子,
吞噬细胞而不产生炎症反应。由此获得的结果
建议将被证明是至关重要的理解再生过程,将是
一般的兴趣,以了解如何在中枢神经系统损伤的反应,
以最小的炎症反应进行。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Diego Javier Rodriguez-Gil其他文献
Diego Javier Rodriguez-Gil的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Diego Javier Rodriguez-Gil', 18)}}的其他基金
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 42.32万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 42.32万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 42.32万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 42.32万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 42.32万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 42.32万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 42.32万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 42.32万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 42.32万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 42.32万 - 项目类别:
Research Grant