Hirao Ayumi, Hojo Yasushi, Murakami Gen, Ito Rina, Hashizume Miki, Murakoshi Takayuki, Uozumi Naonori
Department of Biochemistry, Faculty of Medicine, Saitama Medical University, Moroyama, Iruma, Saitama, Japan.
Department of Liberal Arts, Faculty of Medicine, Saitama Medical University, Moroyama, Iruma, Saitama, Japan.
PLoS One. 2024 May 3;19(5):e0302470. doi: 10.1371/journal.pone.0302470. eCollection 2024.
Network oscillation in the anterior cingulate cortex (ACC) plays a key role in attention, novelty detection and anxiety; however, its involvement in cognitive impairment caused by acute systemic inflammation is unclear. To investigate the acute effects of systemic inflammation on ACC network oscillation and cognitive function, we analyzed cytokine level and cognitive performance as well as network oscillation in the mouse ACC Cg1 region, within 4 hours after lipopolysaccharide (LPS, 30 μg/kg) administration. While the interleukin-6 concentration in the serum was evidently higher in LPS-treated mice, the increases in the cerebral cortex interleukin-6 did not reach statistical significance. The power of kainic acid (KA)-induced network oscillation in the ACC Cg1 region slice preparation increased in LPS-treated mice. Notably, histamine, which was added in vitro, increased the oscillation power in the brain slices from LPS-untreated mice; for the LPS-treated mice, however, the effect of histamine was suppressive. In the open field test, frequency of entries into the center area showed a negative correlation with the power of network oscillation (0.3 μM of KA, theta band (3-8 Hz); 3.0 μM of KA, high-gamma band (50-80 Hz)). These results suggest that LPS-induced systemic inflammation results in increased network oscillation and a drastic change in histamine sensitivity in the ACC, accompanied by the robust production of systemic pro-inflammatory cytokines in the periphery, and that these alterations in the network oscillation and animal behavior as an acute phase reaction relate with each other. We suggest that our experimental setting has a distinct advantage in obtaining mechanistic insights into inflammatory cognitive impairment through comprehensive analyses of hormonal molecules and neuronal functions.
前扣带回皮质（ACC）中的网络振荡在注意力、新奇性检测和焦虑中起关键作用；然而，其在急性全身炎症引起的认知障碍中的作用尚不清楚。为了研究全身炎症对ACC网络振荡和认知功能的急性影响，我们在给予脂多糖（LPS，30μg/kg）后4小时内，分析了小鼠ACC Cg1区域的细胞因子水平、认知表现以及网络振荡。虽然LPS处理的小鼠血清中的白细胞介素-6浓度明显更高，但大脑皮质中白细胞介素-6的增加未达到统计学显著性。在LPS处理的小鼠中，ACC Cg1区域脑片制备中由 kainic acid（KA）诱导的网络振荡功率增加。值得注意的是，体外添加的组胺增加了未用LPS处理的小鼠脑片中的振荡功率；然而，对于用LPS处理的小鼠，组胺的作用是抑制性的。在旷场试验中，进入中心区域的频率与网络振荡功率呈负相关（0.3μM的KA，θ波段（3 - 8Hz）；3.0μM的KA，高γ波段（50 - 80Hz））。这些结果表明，LPS诱导的全身炎症导致ACC中网络振荡增加和组胺敏感性的剧烈变化，同时外周全身促炎细胞因子大量产生，并且这些网络振荡和动物行为的改变作为急性期反应相互关联。我们认为，我们的实验设置在通过对激素分子和神经元功能的综合分析来深入了解炎症性认知障碍的机制方面具有明显优势。
