Role of the cannabinoid receptor 2 (CB2) in neuroinflammation

大麻素受体 2 (CB2) 在神经炎症中的作用

• 批准号: 198462847
• 负责人: Professorin Dr. Judith Alferink
• 金额: --
• 依托单位: Klinik für Psychische Gesundheit
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/198462847?language=en
• 关键词: Role; cannabinoid; receptor; CB2; neuroinflammation

Our previous work demonstrated the impact of the cannabinoid receptor 2 (CB2) in the control of IFN- γ responses and microglial activation during neuroinflammation in chronic pain. Since both immune processes are known to influence the pathogenesis of parasite-induced encephalitis, we also investigated CB2 signaling in cerebral malaria (CM) and Toxoplasma gondii encephalitis (TE). Plasmodium berghei ANKA (PbA)-infected CB2 knockout (Cnr2-/-) mice exhibit enhanced survival, while all wild type (WT) controls succumb to disease. A reduced blood vessel sequestration and an intact blood brain barrier identified in infected Cnr2-/- mice could cause increased resistance. In addition, diminished neuroinflammatory responses occur in Cnr2-/- animals with reduced numbers of CNS-immigrated CD8 T cells and activated myeloid cells. Importantly, therapeutic application of the CB2 antagonist SR122458 confers enhanced CM resistance in C57BL/6 mice. A functional role of CB2 in the immunopathogenesis of TE was further demonstrated in T. gondii-infected Cnr2-/- mice which exhibit enhanced mortality. Here we plan to investigate the underlying CB2-mediated immune mechanisms in parasite encephalitis by assessing Cnr2-/- and bone-marrow-chimeric mice and CB2- based pharmacological approaches. To dissect the specific roles of CB2 signaling in lymphocytes and/or myeloid cells during neuroinflammation, cell-specific CB2 conditional knockout mice will be investigated. We aim to define novel CB2-dependent mechanisms with therapeutic potential involved in the control of neuroinflammatory responses.

我们以前的工作证明了大麻素受体2（CB 2）在慢性疼痛神经炎症过程中控制IFN- γ反应和小胶质细胞活化的影响。由于这两个免疫过程是已知的影响寄生虫引起的脑炎的发病机制，我们还研究了CB 2信号在脑型疟疾（CM）和弓形虫脑炎（TE）。伯氏疟原虫ANKA（PbA）感染的CB 2敲除（Cnr 2-/-）小鼠表现出增强的存活率，而所有野生型（WT）对照都死于疾病。在感染的Cnr 2-/-小鼠中鉴定的减少的血管隔离和完整的血脑屏障可能导致抗性增加。此外，减少的神经炎症反应发生在Cnr 2-/-动物中，CNS-迁移的CD 8 T细胞和活化的骨髓细胞的数量减少。重要的是，CB 2拮抗剂SR 122458的治疗应用赋予C57 BL/6小鼠增强的CM抗性。CB 2在TE免疫发病机制中的功能作用在T.显示出增加的死亡率的刚地氏菌感染的Cnr 2-/-小鼠。在这里，我们计划通过评估Cnr 2-/-和骨髓嵌合小鼠和基于CB 2的药理学方法来研究寄生虫脑炎中CB 2介导的免疫机制。为了剖析CB 2信号传导在神经炎症期间在淋巴细胞和/或骨髓细胞中的特定作用，将研究细胞特异性CB 2条件性敲除小鼠。我们的目的是确定新的CB 2依赖性机制与治疗潜力参与控制神经炎症反应。

项目成果

The cannabinoid receptor 2 is involved in acute rejection of cardiac allografts.

• DOI: 10.1016/j.lfs.2015.02.012
• 发表时间: 2015-10
• 期刊: Life sciences
• 影响因子: 6.1
• 作者: A. Kemter;S. Scheu;N. Hüser;C. Ruland;B. Schumak;Matthias Findeiß;Zhangjun Cheng;V. Assfalg;V. Arolt;A. Zimmer;J. Alferink

Cannabinoid receptor 2 deficiency results in reduced neuroinflammation in an Alzheimer's disease mouse model

• DOI: 10.1016/j.neurobiolaging.2014.09.019
• 发表时间: 2015-02-01
• 期刊: NEUROBIOLOGY OF AGING
• 影响因子: 4.2
• 作者: Schmoele, Anne-Caroline;Lundt, Ramona;Zimmer, Andreas
• 通讯作者: Zimmer, Andreas

The endocannabinoid-CB2 receptor axis protects the ischemic heart at the early stage of cardiomyopathy

• DOI: 10.1007/s00395-014-0425-x
• 发表时间: 2014-07-01
• 期刊: BASIC RESEARCH IN CARDIOLOGY
• 影响因子: 9.5
• 作者: Duerr, Georg D.;Heinemann, Jan C.;Dewald, Oliver
• 通讯作者: Dewald, Oliver