Aging attenuates radiation-induced expression of pro-inflammatory mediators in rat brain

Abstract

The present study was designed to examine the effect of aging on radiation-induced expression of pro-inflammatory mediators in rat brain. Male F344xBN rats (4, 16, and 24 months of age) received either whole brain irradiation with a single dose of 10Gy gamma-rays or sham-irradiation, and were maintained for 4, 8, and 24h post-irradiation. The mRNA expression levels of various pro-inflammatory mediators such as cytokines, adhesion molecules, chemokine, and matrix metalloproteinase were analyzed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). The acute inflammatory responses to irradiation, including overexpression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, monocyte chemoattractant protein-1 (MCP-1), and matrix metalloproteinase-9 (MMP-9) were markedly attenuated in the hippocampus of middle-aged and old rats compared with young groups. Specifically, a significant age-dependent decrease in TNF-alpha expression was detected 8 and 24h after irradiation and a similar age-related attenuation was observed in IL-1beta, ICAM-1, and VCAM-1 expression 4 and 8h post-irradiation. MCP-1 expression was reduced 4h post-irradiation and MMP-9 expression at 8h post-irradiation. These results provide evidence for the first time that radiation-induced pro-inflammatory responses in the brain are suppressed in aged animals.

Fig 1

Effect of aging on mRNA expression of pro-inflammatory cytokines in rat brain in response to whole brain irradiation. F344 x BN rats (4, 16, and 24 months of age; n=4) received either whole brain irradiation with a single dose of 10Gy or sham-irradiation, and were maintained for 4, 8, or 24 h post-irradiation. The mRNA expression levels of TNF-α (A), IL-1β (B), and IL-6 (C) in hippocampus were determined by quantitative real-time RT-PCR. Values represent mean±SEM for each group. *p<0.05 vs. age-matched control; !p<0.05 vs. young rats; #p<0.05 vs. young and middle-aged rats.

Fig 2

Effect of aging on mRNA expression of adhesion molecules in rat brain in response to whole brain irradiation. Experiments were carried out as described in Fig. 1. The mRNA levels of ICAM-1 (A), VCAM-1 (B), and E-selectin (C) in hippocampus were determined by quantitative real-time RT-PCR. Values represent mean±SEM for each group. *p<0.05 vs. age-matched control; !p<0.05 vs. young rats; #p<0.05 vs. young and middle-aged rats.

Fig 3

Effect of aging on MCP-1 mRNA expression in rat brain in response to whole brain irradiation. Experiments were carried out as described in Fig. 1. The mRNA level of MCP-1 was determined by quantitative real-time RT-PCR. Values represent mean±SEM for each group. *p<0.05 vs. age-matched control; !p<0.05 vs. young rats; #p<0.05 vs. young and middle-aged rats.

Fig 4

Effect of aging on MMP-9 mRNA expression in rat brain in response to whole brain irradiation. Experiments were carried out as described in Fig. 1. The mRNA level of MMP-9 was determined by quantitative real-time RT-PCR. Values represent mean±SEM for each group. *p<0.05 vs. age-matched control; !p<0.05 vs. young rats; #p<0.05 vs. young and middle-aged rats.