Intra- and extra-cellular cholesterol transport systems during brain repair and synaptic remodelling in the adult rodent brain

成年啮齿动物大脑修复和突触重塑过程中的细胞内和细胞外胆固醇转运系统

基本信息

  • 批准号:
    RGPIN-2015-03790
  • 负责人:
  • 金额:
    $ 2.19万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2017
  • 资助国家:
    加拿大
  • 起止时间:
    2017-01-01 至 2018-12-31
  • 项目状态:
    已结题

项目摘要

Our team has documented an elegant mechanism by which the injured brain uses the cholesterol and phospholipids released from dead/dying cells to feed surviving neurons with the lipids which are required for the proper rebuilding new synaptic networks. We call this process the cholesterol recycling/remodeling cascade. Our team has already demonstrated that the extracellular transport of cholesterol and phospholipids by apolipoprotein E (apoE), a highly functional lipid transporter, is required andnecessary for the replacement of synaptic networks in response to brain injury or, neurotoxic insult in rodents. In response, cell-surface receptors that recognize apoE-lipoprotein complexes (i.e. HDL) were found to mediate the internalization and redistribution of the cholesterol required for the formation of new sprouts and new synapses. The complete absence of brain apoE or, its main receptor, in knockout mice was shown to compromise i) synaptic integrity with age, ii) lesion-induced synaptic recovery and iii) cognitive performance. Unfortunately, we know very little about the initiation of this cascade; i.e. the transport and packaging of cholesterol and phospholipids from intracellular astroglial compartments towards the apoE-lipoprotein (HDL) assembly line.
我们的团队记录了一种优雅的机制,通过这种机制,受损的大脑使用死亡/濒临死亡的细胞释放的胆固醇和磷脂,向存活的神经元提供脂质,这是正确重建新突触网络所需的。我们将这一过程称为胆固醇循环/重塑级联。我们的团队已经证明,载脂蛋白E(ApoE)是一种高功能的脂质转运蛋白,它在细胞外转运胆固醇和磷脂是啮齿类动物应对脑损伤或神经毒性侮辱而替换突触网络所必需的。相应地,识别载脂蛋白E-脂蛋白复合体(即高密度脂蛋白)的细胞表面受体被发现介导了形成新芽和新突触所需的胆固醇的内化和重新分布。在基因敲除小鼠中,大脑apoE或其主要受体apoE的完全缺失被证明损害了1)突触完整性与年龄,ii)损伤诱导的突触恢复和iii)认知能力。不幸的是,我们对这一级联反应的启动机制知之甚少;即胆固醇和磷脂从细胞内星形胶质细胞隔间向载脂蛋白(HDL)装配线的运输和包装。

项目成果

期刊论文数量(0)
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Poirier, Judes其他文献

Association of PPP2R1A with Alzheimer's disease and specific cognitive domains
  • DOI:
    10.1016/j.neurobiolaging.2019.06.008
  • 发表时间:
    2019-09-01
  • 期刊:
  • 影响因子:
    4.2
  • 作者:
    Miron, Justin;Picard, Cynthia;Poirier, Judes
  • 通讯作者:
    Poirier, Judes
Differential regulation of ABCA1 and ABCG1 gene expressions in the remodeling mouse hippocampus after entorhinal cortex lesion and liver-X receptor agonist treatment
  • DOI:
    10.1016/j.brainres.2014.03.016
  • 发表时间:
    2014-05-08
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Jasmin, Stephanie Belanger;Pearson, Vanessa;Poirier, Judes
  • 通讯作者:
    Poirier, Judes
Association of TLR4 with Alzheimer's disease risk and presymptomatic biomarkers of inflammation
  • DOI:
    10.1016/j.jalz.2019.03.012
  • 发表时间:
    2019-07-01
  • 期刊:
  • 影响因子:
    14
  • 作者:
    Miron, Justin;Picare, Cynthia;Poirier, Judes
  • 通讯作者:
    Poirier, Judes
Social isolation is linked to classical risk factors of Alzheimer's disease-related dementias.
  • DOI:
    10.1371/journal.pone.0280471
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Shafighi, Kimia;Villeneuve, Sylvia;Rosa Neto, Pedro;Badhwar, AmanPreet;Poirier, Judes;Sharma, Vaibhav;Medina, Yasser Iturria;Silveira, Patricia P.;Dube, Laurette;Glahn, David;Bzdok, Danilo
  • 通讯作者:
    Bzdok, Danilo
Characteristics of subjective cognitive decline associated with amyloid positivity.
  • DOI:
    10.1002/alz.12512
  • 发表时间:
    2022-10
  • 期刊:
  • 影响因子:
    14
  • 作者:
    Janssen, Olin;Jansen, Willemijn J.;Vos, Stephanie J. B.;Boada, Merce;Parnetti, Lucilla;Gabryelewicz, Tomasz;Fladby, Tormod;Molinuevo, Jose Luis;Villeneuve, Sylvia;Hort, Jakub;Epelbaum, Stephane;Lleo, Alberto;Engelborghs, Sebastiaan;van der Flier, Wiesje M.;Landau, Susan;Popp, Julius;Wallin, Anders;Scheltens, Philip;Rikkert, Marcel Olde;Snyder, Peter J.;Rowe, Chris;Chetelat, Gael;Ruiz, Agustin;Marquie, Marta;Chipi, Elena;Wolfsgruber, Steffen;Heneka, Michael;Boecker, Henning;Peters, Oliver;Jarholm, Jonas;Rami, Lorena;Tort-Merino, Adria;Binette, Alexa Pichet;Poirier, Judes;Rosa-Neto, Pedro;Cerman, Jiri;Dubois, Bruno;Teichmann, Marc;Alcolea, Daniel;Fortea, Juan;Sanchez-Saudinos, M. Belen;Ebenau, Jarith;Pocnet, Cornelia;Eckerstrom, Marie;Thompson, Louisa;Villemagne, Victor;Buckley, Rachel;Burnham, Samantha;Delarue, Marion;Freund-Levi, Yvonne;Wallin, Asa K.;Ramakers, Inez;Tsolaki, Magda;Soininen, Hilkka;Hampel, Harald;Spiru, Luiza;Tijms, Betty;Ossenkoppele, Rik;Verhey, Frans R. J.;Jessen, Frank;Visser, Pieter Jelle
  • 通讯作者:
    Visser, Pieter Jelle

Poirier, Judes的其他文献

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{{ truncateString('Poirier, Judes', 18)}}的其他基金

Cholesterol-related genes in response to brain deafferentation in normal and transgenic mice
胆固醇相关基因对正常和转基因小鼠脑传入神经阻滞的反应
  • 批准号:
    RGPIN-2020-04702
  • 财政年份:
    2022
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Cholesterol-related genes in response to brain deafferentation in normal and transgenic mice
胆固醇相关基因对正常和转基因小鼠脑传入神经阻滞的反应
  • 批准号:
    RGPIN-2020-04702
  • 财政年份:
    2021
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Cholesterol-related genes in response to brain deafferentation in normal and transgenic mice
胆固醇相关基因对正常和转基因小鼠脑传入神经阻滞的反应
  • 批准号:
    RGPIN-2020-04702
  • 财政年份:
    2020
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Intra- and extra-cellular cholesterol transport systems during brain repair and synaptic remodelling in the adult rodent brain
成年啮齿动物大脑修复和突触重塑过程中的细胞内和细胞外胆固醇转运系统
  • 批准号:
    RGPIN-2015-03790
  • 财政年份:
    2019
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Intra- and extra-cellular cholesterol transport systems during brain repair and synaptic remodelling in the adult rodent brain
成年啮齿动物大脑修复和突触重塑过程中的细胞内和细胞外胆固醇转运系统
  • 批准号:
    RGPIN-2015-03790
  • 财政年份:
    2018
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Intra- and extra-cellular cholesterol transport systems during brain repair and synaptic remodelling in the adult rodent brain
成年啮齿动物大脑修复和突触重塑过程中的细胞内和细胞外胆固醇转运系统
  • 批准号:
    RGPIN-2015-03790
  • 财政年份:
    2016
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Intra- and extra-cellular cholesterol transport systems during brain repair and synaptic remodelling in the adult rodent brain
成年啮齿动物大脑修复和突触重塑过程中的细胞内和细胞外胆固醇转运系统
  • 批准号:
    RGPIN-2015-03790
  • 财政年份:
    2015
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Role of apolipoproteins and ABC transporters during brain reinnervation in the adult mice
载脂蛋白和 ABC 转运蛋白在成年小鼠大脑神经支配中的作用
  • 批准号:
    355917-2009
  • 财政年份:
    2013
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Role of apolipoproteins and ABC transporters during brain reinnervation in the adult mice
载脂蛋白和 ABC 转运蛋白在成年小鼠大脑神经支配中的作用
  • 批准号:
    355917-2009
  • 财政年份:
    2012
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Role of apolipoproteins and ABC transporters during brain reinnervation in the adult mice
载脂蛋白和 ABC 转运蛋白在成年小鼠大脑神经支配中的作用
  • 批准号:
    355917-2009
  • 财政年份:
    2011
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual

相似国自然基金

BET蛋白家族溴结构域抑制剂治疗恶性胰腺导管内乳头状黏液瘤及相关耐药机制的研究
  • 批准号:
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    2017
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    21.0 万元
  • 项目类别:
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Project 3 - Mechanisms of extra- and intra-cellular calcification
项目3——细胞外和细胞内钙化的机制
  • 批准号:
    10628930
  • 财政年份:
    2023
  • 资助金额:
    $ 2.19万
  • 项目类别:
Spatiotemporal models of intra and extra cellular processes
细胞内和细胞外过程的时空模型
  • 批准号:
    RGPIN-2016-04314
  • 财政年份:
    2021
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    $ 2.19万
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    Discovery Grants Program - Individual
Spatiotemporal models of intra and extra cellular processes
细胞内和细胞外过程的时空模型
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    RGPIN-2016-04314
  • 财政年份:
    2020
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    Discovery Grants Program - Individual
Spatiotemporal models of intra and extra cellular processes
细胞内和细胞外过程的时空模型
  • 批准号:
    RGPIN-2016-04314
  • 财政年份:
    2019
  • 资助金额:
    $ 2.19万
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    Discovery Grants Program - Individual
Intra- and extra-cellular cholesterol transport systems during brain repair and synaptic remodelling in the adult rodent brain
成年啮齿动物大脑修复和突触重塑过程中的细胞内和细胞外胆固醇转运系统
  • 批准号:
    RGPIN-2015-03790
  • 财政年份:
    2019
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Intra- and extra-cellular cholesterol transport systems during brain repair and synaptic remodelling in the adult rodent brain
成年啮齿动物大脑修复和突触重塑过程中的细胞内和细胞外胆固醇转运系统
  • 批准号:
    RGPIN-2015-03790
  • 财政年份:
    2018
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Spatiotemporal models of intra and extra cellular processes
细胞内和细胞外过程的时空模型
  • 批准号:
    RGPIN-2016-04314
  • 财政年份:
    2018
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Spatiotemporal models of intra and extra cellular processes
细胞内和细胞外过程的时空模型
  • 批准号:
    RGPIN-2016-04314
  • 财政年份:
    2017
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Intra- and extra-cellular cholesterol transport systems during brain repair and synaptic remodelling in the adult rodent brain
成年啮齿动物大脑修复和突触重塑过程中的细胞内和细胞外胆固醇转运系统
  • 批准号:
    RGPIN-2015-03790
  • 财政年份:
    2016
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
Spatiotemporal models of intra and extra cellular processes
细胞内和细胞外过程的时空模型
  • 批准号:
    RGPIN-2016-04314
  • 财政年份:
    2016
  • 资助金额:
    $ 2.19万
  • 项目类别:
    Discovery Grants Program - Individual
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