The role of cholinergic basal forebrain neurons in adenosine-mediated homeostatic control of sleep: lessons from 192 IgG-saporin lesions.
The role of cholinergic basal forebrain neurons in adenosine-mediated homeostatic control of sleep: lessons from 192 IgG-saporin lesions.
复制标题
DOI：
10.1016/j.neuroscience.2008.08.040
复制
发表时间：
2008-11-11
期刊：
影响因子：
3.3
通讯作者：
Basheer R
中科院分区：
文献类型：
--
作者：
Kalinchuk AV;McCarley RW;Stenberg D;Porkka-Heiskanen T;Basheer R
当前高度关注和争议的主题是稳态睡眠反应的基础，即睡眠剥夺（SD）后非快速眼动（NREM）睡眠和NREM-δ活动的增加。腺苷在SD期间在基底前脑（BF）的胆碱能神经中积累，被认为是重要的稳态睡眠因子之一。提示腺苷的睡眠诱导作用是通过抑制BF的觉醒神经元，包括胆碱能神经元来介导的。在这里，我们研究了SD诱导的腺苷释放，稳态睡眠反应和存活的胆碱能神经元在BF后注射免疫毒素192 IgG-皂草素（皂草素）在啮齿动物之间的关联。我们将SD诱导的BF中腺苷水平和稳态睡眠反应与局部注射皂草素后2周以及脑室内（ICV）注射皂草素后2周和3周的胆碱能细胞损失相关。局部注射皂草素两周后，有88%的胆碱能细胞损失，加上几乎完全取消SD诱导的腺苷增加BF，稳态睡眠反应，和BF腺苷输注的睡眠诱导作用。两周后，ICV注射皂草素有59%的胆碱能细胞损失，与SD诱导的腺苷水平显着增加BF和完整的睡眠反应。ICV皂草素注射后3周，胆碱能细胞损失87%，SD诱导的BF腺苷增加和稳态反应几乎完全消除，这意味着ICV皂草素损伤的时间过程是解释实验结果的关键变量。两者合计，这些结果强烈表明，胆碱能神经元的BF是重要的SD诱导的腺苷增加，以及其睡眠诱导作用，并发挥主要的，但不是唯一的，在睡眠稳态的作用。
A topic of high current interest and controversy is the basis of the homeostatic sleep response, the increase in non-rapid-eye-movement (NREM) sleep and NREM-delta activity following sleep deprivation (SD). Adenosine, which accumulates in the cholinergic basal forebrain (BF) during SD, has been proposed as one of the important homeostatic sleep factors. It is suggested that sleep-inducing effects of adenosine are mediated by inhibiting the wake-active neurons of the BF, including cholinergic neurons. Here we examined the association between SD-induced adenosine release, the homeostatic sleep response and the survival of cholinergic neurons in the BF after injections of the immunotoxin 192 IgG-saporin (saporin) in rodents. We correlated SD-induced adenosine level in the BF and the homeostatic sleep response with the cholinergic cell loss 2 weeks after local saporin injections into the BF, as well as 2 and 3 weeks after intracerebroventricular (ICV) saporin injections. Two weeks after local saporin injection there was an 88% cholinergic cell loss, coupled with nearly complete abolition of the SD-induced adenosine increase in the BF, the homeostatic sleep response, and the sleep-inducing effects of BF adenosine infusion. Two weeks after ICV saporin injection there was a 59% cholinergic cell loss, correlated with significant increase in SD-induced adenosine level in the BF and an intact sleep response. Three weeks after ICV saporin injection there was an 87% cholinergic cell loss, nearly complete abolition of the SD-induced adenosine increase in the BF and the homeostatic response, implying that the time course of ICV saporin lesions is a key variable in interpreting experimental results. Taken together, these results strongly suggest that cholinergic neurons in the BF are important for the SD-induced increase in adenosine as well as for its sleep-inducing effects and play a major, although not exclusive, role in sleep homeostasis.
登录
查看更多内容
影响因子：
3.4
作者：
Berntson, GG;Shafi, R;Sarter, M
通讯作者：
Sarter, M
DOI：
10.1016/s0169-328x(99)00219-3
发表时间：
1999-11-10
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Basheer, R;Porkka-Heiskanen, T;McCarley, RW
通讯作者：
McCarley, RW
影响因子：
3.3
作者：
Arrigoni, E.;Chamberlin, N. L.;McCarley, R. W.
通讯作者：
McCarley, R. W.
影响因子：
2.5
作者：
FRANKEN, P;TOBLER, I;BORBELY, AA
通讯作者：
BORBELY, AA
影响因子：
3.4
作者：
Kalinchuk, A. V.;Stenberg, D.;Porkka-Heiskanen, T.
通讯作者：
Porkka-Heiskanen, T.