Central responses to peripheral inflammation may include decreased expression of key apoptotic protease caspase-3 in brainstem

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Abstract

Microglia activation by proinflammatory stimuli, including lipopolysaccharide (LPS), is considered among the risk factors for neurodegeneration, but the LPS treatment may also have a neuroprotective effect, which leads to further analysis of the relationship between microglial activation and regulators of cell death. In the present work, a comparative study was carried out on proteins expression of marker for activated microglia Iba-1 and the apoptotic executor protease caspase-3 in the brainstem and prefrontal cortex of rats injected intraperitoneally with endotoxin at different doses and schedules. One day after LPS at a dose of 0.5 mg/kg, single, the Iba-1 and caspase-3 expression in both structures did not differ from control values. Endotoxin administration fourfold at the same dose over 7 days (once every 2 days) led one day after the last injection to a significant increase in the Iba-1 level in the brainstem, which was accompanied by a significant decrease in the expression of caspase-3. The same effects in this structure were observed 7 days after a single injection of LPS at a higher dose of 5 mg/kg. In a 7-day experiment, in contrast to the brainstem, no changes in caspase-3 expression were found in the frontal cortex, and an increase in Iba-1 expression was observed only after a single injection of LPS at a high dose. The detected decrease of caspase-3 level in the brain stem under neuroinflammatory conditions may reflect the development of neuroprotective processes, especially important for the structure responsible for such key body functions as respiration, blood pressure and heartbeat.

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About the authors

A. V. Bannova

Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Author for correspondence.
Email: anitik@bionet.nsc.ru
Russian Federation, Novosibirsk

G. T. Shishkina

Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Email: anitik@bionet.nsc.ru
Russian Federation, Novosibirsk

N. N. Dygalo

Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences

Email: anitik@bionet.nsc.ru
Russian Federation, Novosibirsk

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2. Fig. 1. Experimental design. Adult male rats were intraperitoneally injected with LPS at doses of 0.5 mg/kg (once and four times, once every 2 days for 7 days, the animals were withdrawn from the experiment 24 hours after the last injection) and 5 mg/kg (once, the animals were withdrawn from the experiment 7 days after the injection of the drugs). Control animals received corresponding injections of saline.

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3. Fig. 2. Levels of Iba-1 (a) and active caspase-3 (b) proteins in the brainstem of adult rats after peripheral administration of LPS at different doses and modes. M ± m, expressed in arbitrary units relative to the β-actin protein level, n = 5–6 animals per group. * — p < 0.05 compared to the group that received a saline injection (one-way ANOVA, LSD criterion).

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4. Fig. 3. Levels of Iba-1 (a) and active caspase-3 (b) proteins in the prefrontal cortex of adult rats after peripheral administration of LPS at different doses and modes. M ± m, expressed in arbitrary units relative to the β-actin protein level, n = 5–6 animals per group. * — p < 0.05 compared to the group that received a saline injection (one-way ANOVA, LSD criterion).

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