An amorphous formula of curcumin (CUR) has shown to enable an improved bioavailability after ingestion. The aim of this study was to investigate the hypothesis that exogenously administered CUR has an advantage in ameliorating post-traumatic stress disorder at low doses. To this end, Long-Evans rats were dietary exposed to CUR at 0.1% or 0.5% from gestational day 6 to postnatal day (PND) 74 or 77. Offspring exposed to 0.1% CUR revealed facilitation of anti-anxiety-like behavior in the open field test and fear-extinction learning tested during PND 62 to 74, increases in hippocampal granule cells expressing immediate-early gene proteins and a decrease in prelimbic cortical neurons expressing phosphorylated extracellular signal-regulated kinase 1/2 after the last trial of the fear-extinction learning test on PND 74. The constitutive gene expression levels of Gria1, Gria2, Grin2d, Slc17a6, and Slc17a7 were altered in the hippocampal dentate gyrus and amygdala on PND 77. These results suggest alterations in synaptic plasticity to strengthen neural circuits in promoting the behavioral effects by 0.1%-CUR. In contrast, 0.5% CUR revealed a lack of any of the changes in behavioral tests that were observed at 0.1%; however, this dose upregulated oxidative stress and neuroinflammation-related genes in the hippocampal dentate gyrus, and increased neural stem cells and proliferation activity of the subgranular zone in the dentate gyrus. These results suggest a possible preventive use of CUR at low doses in mitigating some stress disorders; however, excessively absorbed doses may prevent behavioral changes by inducing neuroinflammation that affects hippocampal neurogenesis involving neural stem cells.

中文翻译：

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从发育阶段持续暴露于无定形姜黄素配方促进大鼠的抗焦虑样行为和恐惧消退学习

姜黄素 (CUR) 的无定形配方已显示可提高摄入后的生物利用度。本研究的目的是调查外源性 CUR 在改善低剂量的创伤后应激障碍方面具有优势的假设。为此，Long-Evans 大鼠从妊娠第 6 天到产后第 74 天或第 77 天，以 0.1% 或 0.5% 的剂量暴露于 CUR。暴露于 0.1% CUR 的后代显示出促进抗焦虑样行为的在 PND 62 至 74 期间进行的野外测试和恐惧消退学习测试，在最后一次恐惧试验后，表达即时早期基因蛋白的海马颗粒细胞增加，表达磷酸化细胞外信号调节激酶 1/2 的前缘皮质神经元减少- PND 74 上的消光学习测试。Gria1、Gria2、Grin2d、Slc17a6 和 Slc17a7 的组成型基因表达水平在 PND 77 的海马齿状回和杏仁核中发生改变。这些结果表明突触可塑性的改变以加强神经回路，将行为影响提高 0.1%-CUR . 相比之下，0.5% 的 CUR 显示在行为测试中没有任何变化，这在 0.1% 时观察到；然而，该剂量上调了海马齿状回中的氧化应激和神经炎症相关基因，并增加了神经干细胞和齿状回颗粒下区的增殖活性。这些结果表明，在减轻某些应激障碍方面，可能会预防性地使用低剂量的 CUR；然而，