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母体免疫激活在精神分裂症大鼠模型中诱发性别依赖性行为差异。

Maternal immune activation induces sex-dependent behavioral differences in a rat model of schizophrenia.

作者信息

Liu Yunxia, Hang Xiaoyi, Zhang Yijie, Fang Yilin, Yuan Shanfang, Zhang Yi, Wu Bin, Kong Yan, Kuang Zihe, Sun Wenjun

机构信息

The Third Clinical Medical College, Beijing University of Chinese Medicine, Beijing, China.

College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

出版信息

Front Psychiatry. 2024 Apr 10;15:1375999. doi: 10.3389/fpsyt.2024.1375999. eCollection 2024.

Abstract

BACKGROUND

Maternal immune activation (MIA) is a mature means to construct a schizophrenia model. However, some preclinical studies have reported that a MIA-induced schizophrenia model seemed to have gender heterogeneity in behavioral phenotype. On the other hand, the MIA's paradigms were diverse in different studies, and many details could affect the effect of MIA. To some extent, it is not credible and scientific to directly compare the gender differences of different MIA programs. Therefore, it is necessary to study whether the sex of the exposed offspring leads to behavioral differences on the premise of maintaining a consistent MIA mode.

METHODS

An animal model of schizophrenia was established by the administration of 10 mg/kg Poly (I: C) when dams were on day 9 of gestation. Then, a number of female and male offspring completed a series of behavioral tests during postnatal days 61-75.

RESULTS

Compared with the female control group ( = 14), female MIA offspring ( = 12) showed a longer movement distance ( = 1.07, < 0.05) and higher average speed ( = 1.08, < 0.05) in the open field test (OFT). In the Y maze test, the percentage of entering the novel arm of female MIA offspring was lower ( = 0.92, < 0.05). Compared with the male control group ( = 14), male MIA offspring ( = 13) displayed less movement distance ( = 0.93, < 0.05) and a lower average speed ( = 0.94, < 0.05) in the OFT. In the Y maze test, the proportion of exploration time in the novel arm of male MIA offspring was lower ( = 0.96, < 0.05). In the EPM, male MIA offspring showed less time ( = 0.85, < 0.05) and a lower percentage of time spent in the open arms ( = 0.85, < 0.05). Male MIA offspring also had a lower PPI index (76 dB + 120 dB, = 0.81, < 0.05; 80 dB + 120 dB, = 1.45, < 0.01).

CONCLUSIONS

Our results showed that the behavioral phenotypes induced by prenatal immune activation were highly dependent on the sex of the offspring.

摘要

背景

母体免疫激活(MIA)是构建精神分裂症模型的一种成熟方法。然而,一些临床前研究报告称,MIA诱导的精神分裂症模型在行为表型上似乎存在性别异质性。另一方面,不同研究中MIA的范式各不相同,许多细节可能会影响MIA的效果。在某种程度上,直接比较不同MIA方案的性别差异是不可信和不科学的。因此,有必要在保持一致的MIA模式的前提下,研究暴露后代的性别是否会导致行为差异。

方法

在母鼠妊娠第9天时,通过给予10mg/kg聚肌苷酸-聚胞苷酸(Poly (I: C))建立精神分裂症动物模型。然后,一些雌性和雄性后代在出生后第61至75天完成了一系列行为测试。

结果

在旷场试验(OFT)中,与雌性对照组(n = 14)相比,雌性MIA后代(n = 12)表现出更长的移动距离(t = 1.07,P < 0.05)和更高的平均速度(t = 1.08,P < 0.05)。在Y迷宫试验中,雌性MIA后代进入新臂的百分比更低(t = 0.92,P < 0.05)。与雄性对照组(n = 14)相比,雄性MIA后代(n = 13)在OFT中表现出更少的移动距离(t = 0.93,P < 0.05)和更低的平均速度(t = 0.94,P < 0.05)。在Y迷宫试验中,雄性MIA后代在新臂中的探索时间比例更低(t = 0.96,P < 0.05)。在高架十字迷宫(EPM)中,雄性MIA后代在开放臂中花费的时间更少(t = 0.85,P < 0.05),且在开放臂中花费时间的百分比更低(t = 0.85,P < 0.05)。雄性MIA后代的预脉冲抑制(PPI)指数也更低(76dB + 120dB,t = 0.81,P < 0.05;80dB + 120dB,t = 1.45,P < 0.01)。

结论

我们的结果表明,产前免疫激活诱导的行为表型高度依赖于后代的性别。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d85c/11040086/9fb1eaa8426f/fpsyt-15-1375999-g001.jpg

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