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妊娠相关的氧化应激和炎症与母体神经元活动或记忆功能受损无关。

Pregnancy-associated oxidative stress and inflammation are not associated with impaired maternal neuronal activity or memory function.

作者信息

Bradshaw Jessica L, Wilson E Nicole, Gardner Jennifer J, Mabry Steve, Tucker Selina M, Rybalchenko Nataliya, Vera Edward, Goulopoulou Styliani, Cunningham Rebecca L

出版信息

bioRxiv. 2024 Jan 27:2024.01.26.577461. doi: 10.1101/2024.01.26.577461.

Abstract

Pregnancy is associated with neural and behavioral plasticity, systemic inflammation, and oxidative stress. Yet, the impact of systemic inflammation and oxidative stress on maternal neural and behavioral plasticity during pregnancy are unclear. We hypothesized that the maternal hippocampal CA1, a brain region associated with cognition, would be protected from pregnancy-associated systemic elevations in inflammation and oxidative stress, mediating stable peripartum cognitive performance. Cognitive performance was tested using novel object recognition (recollective memory), Morris water maze (spatial memory), and open field (anxiety-like) behavior tasks in female Sprague-Dawley rats of varying reproductive states [non-pregnant (nulliparous), pregnant (near term), and two months post-pregnancy (primiparous); n = 7-8/group]. Plasma and CA1 proinflammatory cytokines were measured using a MILLIPLEX® magnetic bead assay. Plasma oxidative stress was measured via advanced oxidation protein products (AOPP) assay. CA1 markers of oxidative stress, neuronal activity, and apoptosis were quantified via western blotting. Our results demonstrate CA1 oxidative stress-associated markers were elevated in pregnant compared to nulliparous rats ( ≤ 0.017) but were equivalent levels in pregnant and primiparous rats. In contrast, reproductive state did not impact CA1 inflammatory cytokines, neuronal activity, or apoptosis. Likewise, there was no effect of reproductive state on recollective or spatial memory. Even so, spatial learning was impaired ( ≤ 0.007) while anxiety-like behavior ( ≤ 0.034) was reduced in primiparous rats. Overall, our data suggest maternal hippocampal CA1 is protected from systemic inflammation but vulnerable to peripartum oxidative stress. Thus, peripartum oxidative stress elevations, such as in pregnancy complications, may contribute to peripartum neural and behavioral plasticity.

摘要

妊娠与神经和行为可塑性、全身炎症及氧化应激相关。然而,孕期全身炎症和氧化应激对母体神经和行为可塑性的影响尚不清楚。我们推测,与认知相关的脑区——母体海马CA1区,会免受孕期相关的全身炎症和氧化应激升高的影响,从而介导稳定的围产期认知表现。我们使用新颖物体识别(回忆性记忆)、莫里斯水迷宫(空间记忆)和旷场(焦虑样)行为任务,对处于不同生殖状态的雌性斯普拉格-道利大鼠[未孕(未产)、怀孕(接近足月)和产后两个月(初产);每组n = 7 - 8只]的认知表现进行了测试。使用MILLIPLEX®磁珠分析法测量血浆和CA1区促炎细胞因子。通过晚期氧化蛋白产物(AOPP)分析法测量血浆氧化应激。通过蛋白质免疫印迹法对CA1区氧化应激、神经元活动和细胞凋亡的标志物进行定量分析。我们的结果表明,与未孕大鼠相比,怀孕大鼠的CA1区氧化应激相关标志物升高(≤0.017),但怀孕大鼠和初产大鼠的水平相当。相比之下,生殖状态并未影响CA1区炎性细胞因子、神经元活动或细胞凋亡。同样,生殖状态对回忆性或空间记忆也没有影响。即便如此,初产大鼠的空间学习能力受损(≤0.007),而焦虑样行为减少(≤0.034)。总体而言,我们的数据表明,母体海马CA1区可免受全身炎症影响,但在围产期易受氧化应激影响。因此,围产期氧化应激升高,如在妊娠并发症中出现的情况,可能会导致围产期神经和行为可塑性的变化。

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