Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerova str., 5A, Moscow, 117485, Russia.
Metab Brain Dis. 2012 Dec;27(4):431-41. doi: 10.1007/s11011-012-9328-4. Epub 2012 Jul 27.
Effects of a chronic combined unpredictable stress on activities of two cell death-related proteases, calpain and cathepsin B, were studied along with indices of nitrergic system in rat brain structures. Male Wistar rats were subjected to a 2-week-long combined stress (combination of unpaired flash light and moderate footshock associated with a white noise session). Stress resulted in a significant loss in the body and thymus weight and increased defecation in the open field test, though neither motor and exploratory activity, nor plasma corticosterone differed from the respective control levels. Decreased calpain activity and increased cathepsin B activity were demonstrated in the hippocampus of stressed rats (previously we have shown that caspase-3 activity was significantly suppressed in the brain of rats subjected to same type of stress). A significant reduction in the number of NOS-containing neurons was accompanied by a chronic stressinduced decline in NOS activity in the neocortex. Similar changes were observed in the hippocampus. However, levels of NO metabolites were elevated in both structures. Thus, stress-induced structural modifications in the brain may be mediated by disturbances in the nitrergic system and increased lysosomal proteolysis.
慢性复合不可预测应激对两种细胞死亡相关蛋白酶（钙蛋白酶和组织蛋白酶 B）活性的影响以及氮能系统指标在大鼠脑结构中的变化进行了研究。雄性 Wistar 大鼠接受为期 2 周的复合应激（不配对闪光和适度足底电击与白噪声结合）。应激导致体重和胸腺重量显著减轻，在旷场试验中粪便增多，但运动和探索活动以及血浆皮质酮均与相应的对照水平无差异。应激大鼠海马中钙蛋白酶活性降低，组织蛋白酶 B 活性升高（我们之前的研究表明，同种类型的应激会导致大鼠大脑中 caspase-3 活性显著受到抑制）。NOS 阳性神经元数量减少，伴随着新皮质中 NOS 活性的慢性应激诱导下降。在海马中也观察到类似的变化。然而，两种结构中的 NO 代谢物水平升高。因此，应激引起的大脑结构改变可能是由氮能系统紊乱和溶酶体蛋白水解增加介导的。
