The mammalian circadian pacemaker in the suprachiasmatic nucleus (SCN) regulates behavioral and physiological processes in a 24-h cycle. During its development, the SCN can be sensitive to external stimuli which may change the circadian phenotypes in adulthood. Here, we investigated the effects of prenatal exposure to endotoxin lipopolysaccharide (LPS) on the developing rhythms in expression of Per1, Per2, Nr1d1 and Rasd1 along the rostrocaudal axis of the SCN, and on the rhythm of the rate-limiting enzyme in melatonin synthesis, pineal alkylamine N-acetyltransferase (AA-NAT). The prenatal LPS treatment induced anxiety-like behavior in adulthood as shown before and affected the rhythmicity of clock genes in the SCN. The major effect was observed for Nr1d1 expression; the least affected gene was Per2. The Nr1d1 in the LPS-treated group was arrhythmic at postnatal day 3, but showed significantly higher amplitude at postnatal day 20 at all SCN parts, similarly to the AA-NAT activity in pineal glands, thus suggesting adaptive flexibility of the developing SCN to immune challenges in early development.

视交叉上核 (SCN) 中的哺乳动物昼夜节律起搏器以 24 小时为周期调节行为和生理过程。在其发育过程中，SCN 可能对外部刺激敏感，这可能会改变成年后的昼夜节律表型。在这里，我们研究了产前暴露于内毒素脂多糖 (LPS) 对Per1、Per2、Nr1d1和Rasd1表达发育节律的影响沿着 SCN 的 rostrocaudal 轴，以及褪黑激素合成中的限速酶松果体烷基胺 N-乙酰转移酶 (AA-NAT) 的节律。如前所述，产前 LPS 治疗会在成年期诱导焦虑样行为，并影响 SCN 中时钟基因的节律性。观察到Nr1d1表达的主要影响；受影响最小的基因是Per2。LPS 治疗组的Nr1d1在出生后第 3 天出现心律失常，但在出生后第 20 天在所有 SCN 部分显示出显着更高的振幅，类似于松果体中的 AA-NAT 活性，因此表明发育中的 SCN 对免疫的适应性灵活性早期发展的挑战。