Shibuki K, Kimura S, Wakatsuki H
Department of Neurophysiology, Brain Research Institute, Niigata University, Asahi-machi, Niigata 951-8585, Japan.
Eur J Neurosci. 2001 Feb;13(3):609-16. doi: 10.1046/j.0953-816x.2000.01413.x.
Carbon monoxide (CO) suppresses brain functions at doses lower than that suppressing oxygen (O(2)) supply to the brain, and the cerebellum is one of the sites most susceptible to the neurotoxic effects of CO. We investigated the effects of CO on the induction of cerebellar long-term depression (LTD) in the synapses between parallel fibres (PFs) and Purkinje cells. CO, at concentrations between 8 nM and 5 microM, exhibited almost no effect on synaptic responses in Purkinje cells, O(2) consumption and NO release from PFs in rat cerebellar slices. However, the induction of LTD was significantly suppressed by CO at concentrations between 40 and 200 nM. The suppressive effect of 40 nM CO was antagonized by 10 microM NOR3, an NO donor. In contrast, CO exhibited no clear effect on the induction of LTD at concentrations between 1 and 5 microM. The induction of LTD, suppressed by 10 microM N(G)-nitro-L-arginine, an inhibitor of NO synthase, was not restored by 5 microM CO. CO is not only a neurotoxic substance but also a candidate for an intercellular messenger. delta-Aminolevulinate (30 microM), a substance facilitating endogenous CO production, suppressed the induction of LTD, and the effect of delta-aminolevulinate was antagonized by 10 microM NOR3. These findings suggest that CO may have a suppressive effect on the induction of cerebellar LTD at nanomolar concentrations, probably via its effects on NO/cGMP signalling.
一氧化碳（CO）在低于抑制大脑氧气（O₂）供应的剂量下就能抑制大脑功能，而小脑是对CO神经毒性作用最敏感的部位之一。我们研究了CO对平行纤维（PFs）与浦肯野细胞之间突触中小脑长时程抑制（LTD）诱导的影响。浓度在8 nM至5 μM之间的CO对大鼠小脑切片中浦肯野细胞的突触反应、O₂消耗以及PFs释放NO几乎没有影响。然而，浓度在40至200 nM之间的CO能显著抑制LTD的诱导。40 nM CO的抑制作用可被10 μM的NO供体NOR3拮抗。相反，浓度在1至5 μM之间的CO对LTD的诱导没有明显影响。10 μM的NO合酶抑制剂N(G)-硝基-L-精氨酸抑制的LTD诱导，5 μM CO不能使其恢复。CO不仅是一种神经毒性物质，也是一种细胞间信使的候选物质。δ-氨基乙酰丙酸（30 μM）是一种促进内源性CO产生的物质，它抑制LTD的诱导，且δ-氨基乙酰丙酸的作用可被10 μM NOR3拮抗。这些发现表明，CO可能在纳摩尔浓度下对小脑LTD的诱导具有抑制作用，可能是通过其对NO/cGMP信号通路的影响。
