Potential role of inducible nitric oxide synthase in the sleep-wake states occurrence in old rats
Potential role of inducible nitric oxide synthase in the sleep-wake states occurrence in old rats
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DOI：
10.1016/j.neuroscience.2005.05.064
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Gharib, A
中科院分区：
文献类型：
--
作者：
Clément, P;Sarda, N;Gharib, A
现在大量证据表明，诱导型一氧化氮合酶与衰老过程中的氧化应激之间存在关联。由于诱导型一氧化氮合酶在与衰老相关的睡眠障碍中所起的作用仍未被探索，我们使用测谎、生化、伏安和免疫组织化学技术比较了老年大鼠（20-24个月）和成年大鼠（3-5个月）中诱导型一氧化氮合酶的参与情况。实验在基础条件下或在全身注射选定的诱导型一氧化氮合酶抑制剂后进行。我们发现，2-氨基-5,6-二氢-6-甲基-4H-1,3-噻嗪（10 mg/kg，腹腔注射）或氨基胍（400 mg/kg，腹腔注射）能够抑制老年大鼠的快速眼动睡眠并诱导慢波睡眠的延迟增强。这些影响并未发生在成年动物身上。在额叶皮层、背侧被盖和背中缝核内，老年大鼠的基础诱导型一氧化氮合酶活性比成年大鼠高85-200%。相比之下，两组的神经元一氧化氮合酶活性没有变化。 2-氨基-5,6-二氢-6-甲基-4H-1,3-噻嗪给药显着降低诱导型一氧化氮合酶活性（根据大脑区域70-80%），与年龄无关，但显着降低老年大鼠皮质一氧化氮的释放。最后，在额叶皮层和中缝背侧，免疫组织化学分析显示，仅在老年动物中才出现诱导型一氧化氮合酶阳性细胞。这些数据支持这样的观点：诱导型一氧化氮合酶产生的一氧化氮在衰老过程中触发和维持快速动眼睡眠中发挥作用。 (c) 2005 年由 Elsevier Ltd 代表 IBRO 出版。
Extensive evidences now suggest that an association between inducible nitric oxide synthase and oxidative stress takes place during aging. Since the part played by inducible nitric oxide synthase in the sleep impairments associated with aging still remains unexplored, we compared its involvement in old rats (20-24 months) versus adult ones (3-5 months) using polygraphic, biochemical, voltammetric and immunohistochemical techniques. The experiments were conducted either in basal condition or after a systemic injection of selected inducible nitric oxide synthase inhibitors. We found that 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (10 mg/kg, i.p.) or aminoguanidine (400 mg/kg, i.p.) was capable to suppress rapid-eye-movement sleep and induce a delayed enhancement in slow-wave sleep in old rats. These effects did not occur in adult animals. Within the frontal cortex, the laterodorsal tegmentum and dorsal raphe nuclei, the basal inducible nitric oxide synthase activity was 85-200% higher in old rats than in adult ones. In contrast, the neuronal nitric oxide synthase activity did not vary in both groups. 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine administration significantly reduced inducible nitric oxide synthase activity (70-80% according to the brain areas) independently of age, but significantly decreased the cortical nitric oxide release in old rats. Finally, in frontal cortex and dorsal raphe immunohistochemical analysis showed inducible nitric oxide synthase-positive cells again only in old animals. These data support the idea that nitric oxide produced by inducible nitric oxide synthase plays a role in the triggering and maintenance of rapid-eye-movement sleep during aging. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.