小鼠腹内侧前额叶皮层昼夜脊柱可塑性的糖皮质激素调节,Journal of Neuroendocrinology

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小鼠腹内侧前额叶皮层昼夜脊柱可塑性的糖皮质激素调节
Journal of Neuroendocrinology ( IF 3.3 ) Pub Date : 2022-11-07 , DOI: 10.1111/jne.13212
Alex M Miller ₁ , Renata M Daniels ₁ , Julietta A Sheng ₁ , T John Wu ₂ , Robert J Handa ₁

Affiliation

腹内侧前额叶皮层 (vmPFC) 调节恐惧获得、恐惧消退、情绪和 HPA 轴功能。多个大脑区域在学习、长期增强 (LTP) 和树突形态方面表现出时间依赖性变化。糖皮质激素与应激情况下树突结构的调节有关。还已知糖皮质激素通过上调Per1转录来调节分子钟夹带。在本研究中，C57BL/6 N 小鼠在一天中的三个不同时间被处死（ZT3、ZT12 和 ZT16，在 ZT12 时熄灯），并使用液滴数字 (dd) 在边缘下和前边缘 vmPFC 子区域中测量 Per1 mRNA表达从肾上腺切除术或假手术恢复 10 天后进行 PCR。假小鼠显示边缘下 (IL) 和边缘前 (PL) 皮层中的Per1节律性，峰值表达发生在 ZT12。肾上腺切除小鼠显示Per1减少IL 和 PL 中 ZT12 的振幅，表明 vmPFC 分子钟受昼夜糖皮质激素振荡的影响。Thy1-eGFP 小鼠用于可视化和量化 ZT 3、12 和 16 深层锥体树突上的树突棘密度。PL 和 IL 中的脊柱密度在光（非活动）和黑暗（活动）阶段之间表现出变化，在 ZT16 观察到峰值脊柱密度，在 ZT3 观察到波谷脊柱密度。脊柱密度的这些变化仅限于细长和粗短型脊柱的变化。为了确定脊柱密度的变化是否受糖皮质激素振荡的调节，在活动期 (ZT10) 开始前 2 小时每天给予 11β-羟化酶抑制剂美替拉酮，持续 7 天。美替拉酮给药可阻断 ZT16 处血浆皮质酮的昼夜峰值和 IL 和 PL 中的峰值脊柱密度。这些结果表明 vmPFC 分子钟基因和树突棘昼夜节律取决于完整的昼夜糖皮质激素振荡。

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Glucocorticoid regulation of diurnal spine plasticity in the murine ventromedial prefrontal cortex

The ventromedial prefrontal cortex (vmPFC) regulates fear acquisition, fear extinction, mood, and HPA axis function. Multiple brain regions exhibit time-of-day dependent variations in learning, long term potentiation (LTP), and dendritic morphology. Glucocorticoids have been implicated in the regulation of dendritic structure in the context of stress. Glucocorticoids are also known to regulate molecular clock entrainment via upregulation of Per1 transcription. In the present study, C57BL/6 N mice were sacrificed at three distinct times of day (ZT3, ZT12, and ZT16, lights off at ZT12) and Per1 mRNA expression was measured in the infralimbic and prelimbic vmPFC subregions using droplet digital (dd) PCR after recovering from adrenalectomy or sham surgery for 10 days. Sham mice showed Per1 rhythmicity in both infralimbic (IL) and prelimbic (PL) cortex, with peak expression occurring at ZT12. Adrenalectomized mice showed reductions in Per1 amplitude at ZT12 in both IL and PL, suggesting that the vmPFC molecular clock is entrained by diurnal glucocorticoid oscillations. Thy1-eGFP mice were used to visualize and quantify dendritic spine density on deep layer pyramidal dendrites at ZT 3, 12, and 16. Spine density in both PL and IL exhibited changes between the light (inactive) and dark (active) phases, with peak spine density observed at ZT16 and trough spine density observed at ZT3. These changes in spine density were restricted to changes in long thin and stubby type spines. To determine if changes in spine density is regulated by glucocorticoid oscillations, the 11β-hydroxylase inhibitor metyrapone was administered 2 h prior to the onset of the active phase (ZT10) daily for 7 days. Metyrapone administration blocked both the diurnal peak of plasma corticosterone and peak spine densities in the IL and PL at ZT16. These results suggest that vmPFC molecular clock gene and dendritic spine diurnal rhythms depend on intact diurnal glucocorticoid oscillations.

更新日期：2022-11-07

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