CEFYBO-CONICET, 1a Cát de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Stress. 2009 Jul;12(4):350-61. doi: 10.1080/10253890802506383.
Nitric oxide (NO) has been involved in many pathophysiological brain processes. Recently, we showed that neuronal nitric oxide synthase (nNOS)-mediated decrease in NO production is involved in memory impairment induced by chronic mild stress (CMS) in BALB/c mice. Two genetically different inbred murine strains, C57BL/6 and BALB/c, show distinct behavioral responses, neurodevelopmental and neurochemical parameters. Here, we perform a comparative study on CMS effects upon learning and memory in both strains, analyzing the role of NO production and its regulation by protein kinase C (PKC). Stressed BALB/c, but not C57Bl/6 mice, showed a poor learning performance in both the open field and passive avoidance inhibitory tasks. Also, CMS induced a diminished NO production by nNOS, associated with an increment in gamma and zeta PKC isoenzymes in BALB/c mice. In C57BL/6 mice, CMS had no effect on NO production, but increased delta and decreased betaI PKC isoforms. In vivo administration of a NOS inhibitor induced behavioral alterations in both strains. These results suggest a differential effect of stress, with BALB/c being more vulnerable to stress than C57BL/6 mice. This effect could be related to a differential regulation of NOS and PKC isoenzymes, pointing to an important role of NO in learning and memory.
一氧化氮（NO）参与了许多病理生理学的脑过程。最近，我们发现神经元型一氧化氮合酶（nNOS）介导的 NO 生成减少与慢性轻度应激（CMS）诱导的 BALB/c 小鼠记忆障碍有关。两种遗传上不同的近交系小鼠，C57BL/6 和 BALB/c，表现出不同的行为反应、神经发育和神经化学参数。在这里，我们对这两种品系的 CMS 对学习和记忆的影响进行了比较研究，分析了 NO 生成及其蛋白激酶 C（PKC）调节的作用。应激的 BALB/c 而不是 C57Bl/6 小鼠在开阔场和被动回避抑制任务中均表现出较差的学习能力。此外，CMS 诱导 nNOS 的 NO 生成减少，与 BALB/c 小鼠中的 gamma 和 zeta PKC 同工酶增加有关。在 C57BL/6 小鼠中，CMS 对 NO 生成没有影响，但增加了 delta 和减少了 betaI PKC 同工型。NOS 抑制剂的体内给药在两种品系中均引起了行为改变。这些结果表明应激的影响具有差异性，BALB/c 比 C57BL/6 小鼠对应激更敏感。这种影响可能与 NOS 和 PKC 同工酶的差异调节有关，表明 NO 在学习和记忆中具有重要作用。
