Table_2_The Effect of LPS and Ketoprofen on Cytokines, Brain Monoamines, and Social Behavior in Group-Housed Pigs.DOCX

Poor health is a risk factor for damaging behaviors, but the mechanisms behind this link are unknown. Injection of pigs with lipopolysaccharide (LPS) can be used to model aspects of poor health. Recent studies have shown that LPS-injected pigs perform more tail- and ear-directed behavior compared to saline-injected pigs and suggest that pro-inflammatory cytokines may play a role in these behaviors. The aims of this study were to test the effect of LPS on the social behavior of pigs and the neurotransmitters and modulators in their brains and to test the effect of a nonsteroidal anti-inflammatory drug on the effects of LPS. Fifty-two female pigs (11–12 weeks) were allocated to four treatments comprising two injections: saline–saline (SS), saline–LPS (SL), ketoprofen–saline (KS), and ketoprofen–LPS (KL). Activity was scan-sampled every 5 min for 6 h after the last injection in the pen. Social behavior was observed continuously in 10 × 15-min bouts between 8 a.m. and 5 p.m. 1 day before (baseline) and 1 and 2 days after the injection. Saliva was analyzed for cortisol and plasma for tryptophan and kynurenine. The frontal cortex, hippocampus, hypothalamus, and brain stem were sampled 72 h after the injection and analyzed for cytokines and monoamines. LPS activated the HPA axis and decreased the activity within 6 h after the injection. Ketoprofen lowered the effect of LPS on cortisol release and attenuated the behavioral signs of sickness in challenged pigs. SL pigs manipulated the ears of their pen mates significantly longer than SS pigs 2 days after the injection. LPS had no observed effect on IFN-γ, TNF-α, and IL-18. At 72 h after the injection, plasma tryptophan was depleted in SL pigs, and tryptophan and kynurenine concentrations in the frontal cortex and brain stem of SL pigs were significantly lower compared to those in SS pigs. Dopamine concentrations in the hypothalamus of SL pigs were significantly lower compared to those in SS pigs. Serotonin concentrations in the hypothalamus and noradrenaline concentrations in the hippocampus of SL pigs were significantly lower compared to those in KL pigs. In conclusion, LPS influenced the different neurotransmitters and modulators in the brain that are hypothesized to play an important role in the regulation of mood and behavior.

健康不佳是损害行为的危险因素，然而，此关联背后的机制尚不明确。通过向猪注射脂多糖（LPS）可以模拟健康不佳的某些方面。近期研究指出，相较于盐水注射的猪，LPS注射的猪表现出更多的尾巴和耳朵指向性行为，并推测促炎性细胞因子可能在其中发挥作用。本研究旨在检验LPS对猪的社会行为及其大脑中的神经递质和调节剂的影响，并检验非甾体抗炎药对LPS效应的影响。将52头（11-12周龄）雌性猪分为四组，每组包含两次注射：盐水-盐水（SS）、盐水-LPS（SL）、酮洛芬-盐水（KS）和酮洛芬-LPS（KL）。在注射后6小时内，每隔5分钟对围栏内的活动进行扫描采样。在注射前1天（基线）及注射后1天和2天，从上午8点至下午5点，连续观察10次15分钟的社会行为。通过分析唾液中的皮质醇和血浆中的色氨酸及犬尿氨酸来检测。在注射后72小时，对额叶皮层、海马体、下丘脑和脑干进行采样，并分析细胞因子和单胺类物质。LPS激活了HPA轴，并在注射后6小时内降低了活动水平。酮洛芬降低了LPS对皮质醇释放的影响，并减轻了受挑战猪的疾病行为迹象。注射后2天，SL猪较SS猪更长时间地操纵其同伴的耳朵。LPS对IFN-γ、TNF-α和IL-18没有观察到明显的影响。在注射后72小时，SL猪的血浆色氨酸耗竭，并且与SS猪相比，SL猪的额叶皮层和脑干中的色氨酸和犬尿氨酸浓度显著降低。SL猪的下丘脑多巴胺浓度较SS猪显著降低。SL猪的下丘脑血清素浓度和海马体去甲肾上腺素浓度均较KL猪显著降低。综上所述，LPS影响了大脑中那些假设在情绪和行为调节中扮演重要角色的不同神经递质和调节剂。