Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus.
Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus.
复制标题
DOI：
10.1093/cercor/bhy258
复制
发表时间：
2018-12-01
期刊：
影响因子：
--
通讯作者：
Leschik J
中科院分区：
文献类型：
--
作者：
Zimmermann T;Maroso M;Beer A;Baddenhausen S;Ludewig S;Fan W;Vennin C;Loch S;Berninger B;Hofmann C;Korte M;Soltesz I;Lutz B;Leschik J
成年小鼠海马中的神经干细胞（NSC）发生在特定的神经原性小生境中，在该小生境中，众多细胞外信号分子会聚以调节NSC增殖以及命运和功能整合。然而，神经干细胞如何对外源性信号作出反应并将其转化为细胞内反应的潜在机制仍然是难以捉摸的。NSC含有功能性内源性大麻素系统，包括大麻素1型受体（CB 1）。为了解释CB 1是否在体内直接或间接调节成体神经发生，我们使用三转基因小鼠对CB 1进行了NSC-specific条件失活。在这里，我们表明，在神经干细胞中缺乏CB 1足以减少干细胞池的增殖，从而导致新生神经元数量的减少。此外，神经元分化受到损害的树突成熟的水平，指向突触后作用的CB 1在体内。神经干细胞特异性CB 1基因敲除后神经发生恶化，导致海马结构长时程增强减少。观察到的细胞和生理变化导致短期空间记忆下降和抑郁样行为增加。这些结果表明，CB 1在神经干细胞及其后代中表达，控制成年小鼠的神经发生，以调节NSC干细胞库、树突形态、活性依赖性可塑性和行为。
Neural stem cells (NSCs) in the adult mouse hippocampus occur in a specific neurogenic niche, where a multitude of extracellular signaling molecules converges to regulate NSC proliferation as well as fate and functional integration. However, the underlying mechanisms how NSCs react to extrinsic signals and convert them to intracellular responses still remains elusive. NSCs contain a functional endocannabinoid system, including the cannabinoid type-1 receptor (CB1). To decipher whether CB1 regulates adult neurogenesis directly or indirectly in vivo, we performed NSC-specific conditional inactivation of CB1 by using triple-transgenic mice. Here, we show that lack of CB1 in NSCs is sufficient to decrease proliferation of the stem cell pool, which consequently leads to a reduction in the number of newborn neurons. Furthermore, neuronal differentiation was compromised at the level of dendritic maturation pointing towards a postsynaptic role of CB1 in vivo. Deteriorated neurogenesis in NSC-specific CB1 knock-outs additionally resulted in reduced long-term potentiation in the hippocampal formation. The observed cellular and physiological alterations led to decreased short-term spatial memory and increased depression-like behavior. These results demonstrate that CB1 expressed in NSCs and their progeny controls neurogenesis in adult mice to regulate the NSC stem cell pool, dendritic morphology, activity-dependent plasticity, and behavior.
登录
查看更多内容
影响因子：
--
作者：
Berg DA;Bond AM;Ming GL;Song H
通讯作者：
Song H
影响因子：
4.7
作者：
Araque A;Castillo PE;Manzoni OJ;Tonini R
通讯作者：
Tonini R
影响因子：
9.8
作者：
Dupret D;Fabre A;Döbrössy MD;Panatier A;Rodríguez JJ;Lamarque S;Lemaire V;Oliet SH;Piazza PV;Abrous DN
通讯作者：
Abrous DN
大麻素对人类脑衍生的神经营养因子（BDNF）水平的初步证据。
影响因子：
3.4
作者：
D'Souza, Deepak Cyril;Pittman, Brian;Perry, Edward;Simen, Arthur
通讯作者：
Simen, Arthur
影响因子：
64.5
作者：
Bonaguidi MA;Wheeler MA;Shapiro JS;Stadel RP;Sun GJ;Ming GL;Song H
通讯作者：
Song H