Central Responses to Peripheral Inflammation May Include Decreased Expression of Key Apoptotic Protease Caspase-3 in the Brainstem

IF 0.6 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Evolutionary Biochemistry and Physiology Pub Date : 2024-06-26 DOI:10.1134/s0022093024030037

A. V. Bannova, G. T. Shishkina, N. N. Dygalo

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Abstract

Microglia activation by proinflammatory stimuli, including lipopolysaccharide (LPS), is considered among the risk factors for neurodegeneration, although LPS treatment may also have a neuroprotective effect, necessitating further analysis of the relationship between microglial activation and cell death regulators. Here, we carried out a comparative analysis of the expression of Iba-1, a protein marker for microglia activation, and caspase-3, a key executor protease of apoptosis, in the brainstem and prefrontal cortex of Wistar rats, depending on LPS dose and schedule of its intraperitoneal administration. One day after a single LPS administration at a dose of 0.5 mg/kg, Iba-1 and caspase-3 expression levels were indistinguishable from control values in both brain structures. A fourfold LPS administration at the same dose over 7 days (once in 2 days) led to a significant increase in Iba-1 expression levels in the brainstem one day after the last injection, which was accompanied by a significant decrease in caspase-3 expression. In the brainstem, the same effects were observed 7 days after a single LPS administration at a higher dose of 5 mg/kg. In the frontal cortex, by contrast, no changes in caspase-3 expression were found in a 7-day experiment, while Iba-1 expression rose only following a single LPS administration at 5 mg/kg. The detected decrease in caspase-3 expression in the brainstem under neuroinflammatory conditions may reflect the development of adaptive neuroprotective processes, particularly important for the brain structure responsible for such key body’s functions as respiration, blood pressure, and heartbeat.

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中枢对外周炎症的反应可能包括脑干中关键凋亡蛋白酶 Caspase-3 的表达减少

摘要包括脂多糖（LPS）在内的促炎性刺激引起的小胶质细胞活化被认为是神经退行性病变的危险因素之一，尽管LPS治疗也可能具有神经保护作用，因此有必要进一步分析小胶质细胞活化与细胞死亡调节因子之间的关系。在这里，我们根据 LPS 的剂量和腹腔给药时间，对 Wistar 大鼠脑干和前额叶皮层中的小胶质细胞活化蛋白标志物 Iba-1 和细胞凋亡关键执行蛋白酶 caspase-3 的表达进行了比较分析。同样剂量的 LPS 在 7 天内注射四次（两天一次），在最后一次注射后一天，脑干中 Iba-1 的表达水平显著增加，同时 caspase-3 的表达水平显著下降。在脑干，单次注射较高剂量（5 毫克/千克）的 LPS 7 天后，也观察到了同样的效应。相比之下，在额叶皮层，7 天的实验中没有发现 caspase-3 表达的变化，而 Iba-1 的表达仅在 5 毫克/千克的单次 LPS 给药后才出现上升。在神经炎症条件下，脑干中检测到的 caspase-3 表达减少可能反映了适应性神经保护过程的发展，这对负责呼吸、血压和心跳等人体关键功能的大脑结构尤为重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Evolutionary Biochemistry and Physiology 生物-进化生物学

自引率

33.30%

发文量

110

审稿时长

6-12 weeks

期刊介绍： Journal of Evolutionary Biochemistry and Physiology publishes original experimental and theoretical and review articles related to evolution of the main forms of metabolism in connection with life origin; comparative and ontogenetic physiology and biochemistry, biochemical evolution of animal world; as well as evolution of functions; morphology, pharmacology, pathophysiology and ecological physiology. The journal welcomes manuscripts from all countries in the English or Russian language.