Anti-ceramidase LCL385 acutely reduces BCL-2 expression in the hippocampus but is not associated with an increase of learned helplessness in rats.
Anti-ceramidase LCL385 acutely reduces BCL-2 expression in the hippocampus but is not associated with an increase of learned helplessness in rats.
复制标题
抗神经酰胺酶 LCL385 急剧降低海马中 BCL-2 的表达，但与大鼠习得性无助的增加无关。
DOI：
10.1016/j.bbr.2008.07.040
复制
发表时间：
2009
影响因子：
2.7
通讯作者：
Hannun,YusufA
中科院分区：
文献类型：
--
作者：
Nahas,Ziad;Jiang,Yan;Zeidan,YoussefH;Bielawska,Alicja;Szulc,Zdzislaw;Devane,Lindsay;Kalivas,Peter;Hannun,YusufA
原位研究的证据支持抗凋亡因子在某些精神药物的抗抑郁反应中的作用。抗神经酰胺酶促凋亡化合物 (LCL385) 的出现为体内测试海马细胞凋亡与习得性无助之间的关系提供了机会。 方法 40 Sprague-Dawley 雄性啮齿动物在使用 LCL385、地昔帕明 (DMI) 或安慰剂 (SAL) 治疗 3 天以上后接受 FST。在 6 分钟测试期间，对行为反应进行计数，包括不动、游泳和攀爬。 Western blot标记用于检测海马的抗凋亡作用。结果单独使用DMI与不动性减少和攀爬增加相关，而单独使用LCL385则显示Bcl-2/β-肌动蛋白比率降低。结论直接调节海马Bcl-2表达与应激大鼠的习得性无助无关。 DMI 和 LCL385 三天给药对行为和抗凋亡措施显示出不同的影响。
Evidence from in situ studies supports the role of anti-apoptotic factors in the antidepressant responses of certain psychotropics. The availability of anti-ceramidase pro-apoptocic compound (LCL385) provides an opportunity to test in vivo the relation between hippocampal apopotosis and learned helplessness.METHOD40 Sprague–Dawley male rodents underwent an FST after a treatment with LCL385, desipramine (DMI), or placebo (SAL) over 3 days. Behavioral responses, including immobility, swimming and climbing were counted during the 6min test. Western blot labeling was used to detect anti-apoptosis in hippocampus.RESULTSDMI alone was associated with reduced immobility and increased climbing whereas LCL385 alone showed a decrease in Bcl-2/β-actin ratio.CONCLUSIONSDirect modulation of Bcl-2 expression in the hippocampus is not associated with learned helplessness in stressed rats. Three-day administration of DMI and LCL385 show divergent effects on behavioral and anti-apoptotic measures.