Serotonin-1A receptor, a psychiatric disease risk factor, influences offspring immunity via sex-dependent genetic nurture

被引:2
|
作者
Chen, Rosa J. [1 ]
Nabila, Anika [1 ]
Phalke, Swati [2 ]
Castro, Danny Flores [2 ]
Toth, Judit Gal [1 ]
Bergin, Paul [1 ]
Bastiaans, Jeroen [3 ]
Stuhlmann, Heidi [3 ]
Pernis, Alessandra B. [2 ]
Toth, Miklos [1 ]
机构
[1] Weill Cornell Med, Dept Pharmacol, New York, NY 10065 USA
[2] Ctr Genom Res Hosp Special Surg, New York, NY 10065 USA
[3] Weill Cornell Med, Cell & Dev Biol, New York, NY 10065 USA
基金
美国国家卫生研究院;
关键词
5-HT1A RECEPTOR; MAJOR DEPRESSION; ANXIETY; BINDING; STRESS; EXPRESSION; ACTIVATION; AUTOIMMUNE; ENDOCRINE; AUTORECEPTOR;
D O I
10.1016/j.isci.2022.105595
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Serotonin-1A receptor (5HT1AR) is highly expressed in corticolimbic regions and its deficit is associated with anxiety and depression. A similar reduction in 5HT1AR heterozygous knockout (Het) mice results in anxiety-like and increased stress-reactivity phenotypes. Here we describe immunological abnormalities in Het females, characterized by an activated state of innate and adaptive immune cells. Het males showed only limited immune dysregulation. Similar immune abnormalities were present in the genetically WT female (F1) but not male offspring of Het mothers, indicating sex-specific immune system abnormalities that are dependent on the mother's 5HT1AR deficit, known as maternal genetic effect or "genetic nurture". Expression profiling of the maternal-fetal interface revealed reduced immune cell invasion to decidua and accelerated trophoblast migration. These data suggest that 5HT1AR deficit, by altering the maternal immune system and midi stational in utero environment, leads to sex-biased outcomes, predominantly immune dysregulation in the female and anxiety-like behavior in the male offspring.
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页数:23
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