CB2 cannabinoid receptors promote mouse neural stem cell proliferation
CB2 cannabinoid receptors promote mouse neural stem cell proliferation
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DOI：
10.1111/j.1460-9568.2007.05322.x
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发表时间：
2007-02-01
影响因子：
3.4
通讯作者：
Molina-Holgado, Eduardo
中科院分区：
文献类型：
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作者：
Molina-Holgado, Francisco;Rubio-Araiz, Ana;Molina-Holgado, Eduardo
神经球是神经干/前体细胞的克隆细胞聚集体，在培养物中作为自由漂浮的簇生长。这些细胞表达的 CB1 大麻素受体的激活可促进增殖。在本研究中，我们研究了 CB2 大麻素受体的表达以及外源性大麻素对神经干/前体细胞增殖的影响。含有巢蛋白阳性和 sn-1 二酰甘油脂肪酶 α 阳性细胞的神经球表达 CB1 和 CB2 受体，并在数代中得以维持。非选择性大麻素激动剂（HU-210，0.5 μM）的应用刺激了溴脱氧尿苷掺入和神经球形成。该作用涉及 CB1 和 CB2 受体，因为神经球形成受到选择性 CB1 [花生四烯基-2'氯乙酰胺/(所有 Z)-N-(2-环乙基)-5,8,11,14-二十碳四烯酰胺 (ACEA)，200 nm 和 1 μM] 或 CB2 (JWH-056，0.5 μM) 激动剂的刺激。此外，CB1或CB2拮抗剂（分别为1μM SR-141716A和SR-144528）阻断基底增殖，表明内源性大麻素与神经球增殖有关。此外，Akt 易位抑制剂 BML-257 (12.5 μM) 减少了大麻素激动剂刺激的增殖，表明磷酸肌醇 3 激酶信号传导的作用。总之，我们的结果表明，大麻素通过磷酸肌醇 3 激酶/Akt 途径刺激作用于 CB1 和 CB2 大麻素受体的神经干/前体细胞的增殖。
Neurospheres are clonal cellular aggregates of neural stem/precursor cells that grow in culture as free-floating clusters. Activation of CB1 cannabinoid receptors, which are expressed by these cells, promotes proliferation. In the present study we investigated the expression of CB2 cannabinoid receptors and the effect of exogenous cannabinoids on neural stem/precursor cell proliferation. Neurospheres containing nestin-positive and sn-1 diacylglycerol lipase alpha-positive cells expressed both CB1 and CB2 receptors, which were maintained through several passages. Application of the non-selective cannabinoid agonist (HU-210, 0.5 mu M) stimulated bromodeoxyuridine incorporation and neurosphere formation. This action involved both CB1 and CB2 receptors as neurosphere formation was stimulated by either selective CB1 [arachidonyl-2'chloroethylamide/(all Z)-N-(2-cycloethyl)-5,8,11,14-eicosatetraenamide (ACEA), 200 nm and 1 mu M] or CB2 (JWH-056, 0.5 mu M) agonists. In addition, CB1 or CB2 antagonists (1 mu M SR-141716A and SR-144528, respectively) blocked basal proliferation, suggesting that endogenous cannabinoids are implicated in neurosphere proliferation. In addition, cannabinoid agonist-stimulated proliferation was reduced by the Akt translocation inhibitor BML-257 (12.5 mu M), suggesting a role for phosphoinositide-3 kinase signalling. Together, our results suggest that cannabinoids stimulate proliferation of neural stem/precursor cells acting on both CB1 and CB2 cannabinoid receptors through a phosphoinositide-3 kinase/Akt pathway.