Epidemiological studies have suggested that traumatic stress increases vulnerability to various mental disorders, such as dementia and psychiatric disorders. While women are more vulnerable than men to depression and anxiety, it is unclear whether endogenous estrogens are responsible for the underlying sex-specific mechanisms. In this study, the aromatase gene heterozygous (Ar+/-) mice were used as an endogenous estrogen deficiency model and age- and sex-matched wild type mice (WT) as controls to study the predator odor 2,3,5-trimethyl-3-thiazoline- (TMT-) induced short- and long-term cognitive and social behavior impairments. In addition, the changes in brain regional neurotransmitters and their associations with TMT-induced changes in behaviors were further investigated in these animals. Our results showed TMT induced immediate fear response in both Ar+/- and WT mice regardless of sexes. TMT induced an acute impairment of novel object recognition memory and long-term social behavior impairment in WT mice, particularly in females, while Ar+/- mice showed impaired novel object recognition in both sexes and TMT-elevated social behaviors, particularly in males. TMT failed to induce changes in the prepulse inhibition (PPI) test in both groups. TMT resulted in a slight increase of DOPAC/DA ratio in the cortex and a significant elevation of this ratio in the striatum of WT mice. In addition, the ratio of HIAA/5-HT was significantly elevated in the cortex of TMT-treated WT mice, which was not found in TMT-treated Ar+/- mice. Taken together, our results indicate that TMT exposure can cause cognitive and social behavior impairments as well as change catecholamine metabolism in WT mice, and endogenous estrogen deficiency might desensitize the behavioral and neurochemical responses to TMT in Ar+/- mice.

中文翻译：

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内源性雌激素影响捕食者气味引起的芳香酶基因缺陷小鼠的认知和社会行为障碍

流行病学研究表明，创伤性压力增加了对各种精神障碍的脆弱性，例如痴呆症和精神障碍。虽然女性比男性更容易抑郁和焦虑，但尚不清楚内源性雌激素是否对潜在的性别特异性机制负责。在这项研究中，芳香酶基因杂合 (Ar+/-) 小鼠被用作内源性雌激素缺乏模型，年龄和性别匹配的野生型小鼠 (WT) 作为对照来研究捕食者气味 2,3,5-三甲基- 3-噻唑啉- (TMT-) 诱导短期和长期认知和社会行为障碍。此外，在这些动物中进一步研究了大脑区域神经递质的变化及其与 TMT 诱导的行为变化的关联。我们的结果表明，无论性别如何，TMT 都能在 Ar+/- 和 WT 小鼠中诱导即时恐惧反应。TMT 导致 WT 小鼠（尤其是雌性）新物体识别记忆的急性损伤和长期社会行为障碍，而 Ar+/- 小鼠在两性和 TMT 升高的社会行为中均表现出新物体识别受损，尤其是雄性。TMT 未能引起两组的前脉冲抑制 (PPI) 测试的变化。TMT 导致皮层中 DOPAC/DA 比率略有增加，而 WT 小鼠纹状体中该比率显着升高。此外，经 TMT 处理的 WT 小鼠皮层中 HIAA/5-HT 的比率显着升高，这在 TMT 处理的 Ar+/- 小鼠中未发现。综合起来，