Neuronal and inducible nitric oxide synthase expressions and activities in the hippocampi and cortices of young adult, aged cognitively unimpaired, and impaired Long-Evans rats
Neuronal and inducible nitric oxide synthase expressions and activities in the hippocampi and cortices of young adult, aged cognitively unimpaired, and impaired Long-Evans rats
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DOI：
10.1016/s0306-4522(02)00082-9
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发表时间：
2002-01-01
期刊：
影响因子：
3.3
通讯作者：
Quirion, R
中科院分区：
文献类型：
--
作者：
Law, A;O'Donnell, J;Quirion, R
一氧化氮（NO）是一种神经信号分子，似乎在学习和记忆中发挥重要作用。由于其氧化特性，这种分子也与神经毒性有关。我们实验室以前的实验已经证明了海马和皮质神经元一氧化氮合酶（NOS）mRNA水平升高，在老年认知未受损和受损的Long-Evans大鼠，这可能代表增加神经元NOS活性，从而导致NO介导的神经毒性，或老年神经元的代偿反应，以维持生理性一氧化氮输出。本研究采用Western blotting和NOS活性测定方法，检测了青年（6月龄）和老年（24-26月龄）Long-Evans大鼠神经元型和诱导型NOS的蛋白表达和活性水平。根据老年动物在Morris水迷宫行为任务中的表现，将其分配为认知未受损或中度认知受损的老年动物。结果表明，老年动物海马和皮层神经元NOS表达明显减少。这些老年动物也表现出增加海马和皮质诱导型NOS的表达。在两个老龄动物组中，认知障碍大鼠海马和皮层神经元的表达显著降低，但海马诱导型NOS的表达显著升高。青年大鼠海马和皮层NOS活性明显高于老年大鼠。老年动物的认知缺陷表现出显着降低海马NOS活性比认知未受损的老年rats.Our数据表明，衰老与神经元的下降，但升高诱导型NOS功能的大脑区域参与学习和记忆。这些现象可能导致在老年动物亚群中观察到的认知缺陷。(C)2002年IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
Nitric oxide (NO) is a neurosignaling molecule that appears to play a significant role in learning and memory. This molecule has also been implicated in neurotoxicity due to its oxidative properties. Previous experiments from our laboratories have demonstrated elevated hippocampal and cortical neuronal nitric oxide synthase (NOS) mRNA levels in aged cognitively unimpaired and impaired Long-Evans rats, which could represent either increased neuronal NOS activity thereby leading to NO-mediated neurotoxicity, or a compensatory response by aged neurones to maintain physiological nitric oxide output. The current study measured the protein expression and activity levels of neuronal and inducible NOS in young adult (6 months) and aged (24-26 months) Long-Evans rats by means of western blotting and NOS activity assay. Aged animals were assigned as either cognitively unimpaired or aged with moderate cognitive impairments based on their performances in the Morris water maze behavioural task. Our results showed that hippocampal and cortical neuronal NOS expressions were significantly decreased in aged animals. These aged animals also exhibited increased hippocampal and cortical inducible NOS expressions. Between the two aged animal groups, cognitively impaired rats showed significantly lower hippocampal and cortical neuronal but higher hippocampal inducible NOS expressions. Young adult rats exhibited significantly higher hippocampal and cortical NOS activities than the aged animals. Aged animals with cognitive deficits showed significantly lower hippocampal NOS activity than cognitively unimpaired aged rats.Our data indicate that aging is associated with a decline in neuronal but elevated inducible NOS functioning in brain areas involved in learning and memory. These phenomena could contribute to the cognitive deficits observed in a subpopulation of aged animals. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.