Mycobacterium vaccae immunization: Inducing resilience to stress during pregnancy in the dam and protecting her offspring

母牛分枝杆菌免疫：增强母鼠对怀孕期间压力的恢复能力并保护其后代

• 批准号: 450542225
• 负责人: Professor Dr. Stefan O. Reber
• 金额: --
• 依托单位: Sektion Molekulare Psychosomatik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/450542225?language=en
• 关键词: Mycobacterium; vaccae; immunization; Inducing; resilience

The postpartum period represents a time with high risk for women to develop mood and anxiety disorders, such as postpartum anxiety (PPA) and postpartum depression (PPD). PPA and PPD, often comorbid, lead to impaired maternal-infant attachment during the critical stages of early brain development and increase the risk of the offspring developing long-term behavioural and emotional problems, including increased vulnerability to mental illness. Although, both the physiological and immunological adaptations that occur throughout the peripartum period and risk factors for PPA and PPD, including stress during pregnancy, are well-known, the mechanisms underlying postpartum mood and anxiety disorders remain elusive. Numerous hypotheses have been postulated to underlie these disorders, such as disruption of ongoing peripartum-associated brain plasticity. Another, less explored hypothesis is that constant immune activation and chronic low grade inflammation in the mother might underlie post-partum mood disorders as well as an increased risk for the offspring to develop somatic and affective disorders later in life, especially when facing chronic severe life stressors (=second hit). Intriguingly, chronic stress interferes with hippocampal neurogenesis and leads to chronic low-grade inflammation. Importantly, and consistent with the above detailed role of immune activation in the development of mood disorders, we have recently shown that immunoregulation induced by repeated preimmunization (s.c.) with a heat-killed preparation of Mycobacterium vaccae (National Collection of Type Cultures (NCTC) 11659), an abundant soil saprophyte with immunoregulatory properties, was able to prevent stress-induced anxiety, spontaneous colitis, and aggravation of dextran sulfate sodium (DSS)-induced colitis, a murine model of inflammatory bowel disease. Therefore, in this proposal we aim to determine whether M. vaccae given prior to mating can protect the dam from the detrimental effects of pregnancy stress on behaviour, HPA axis, inflammatory responses and hippocampal neurogenesis. Further, we will determine whether this can also protect the offspring from the effects of prenatal stress and/or subsequent exposure to chronic psychosocial stress in adulthood. Taken together, this project will determine whether immunoregulatory approaches can protect both the mother and her offspring from consequences of subsequent chronic stress during pregnancy.

产后期是女性情绪和焦虑障碍的高危时期，如产后焦虑(PPA)和产后抑郁(PPD)。PPA和PPD往往并存，在大脑早期发育的关键阶段会导致母婴依恋受损，并增加后代出现长期行为和情感问题的风险，包括更容易患上精神疾病。虽然，发生在整个围产期的生理和免疫适应以及PPA和PPD的危险因素，包括怀孕期间的压力，都是众所周知的，但产后情绪和焦虑障碍的机制仍然不清楚。许多假说被认为是这些疾病的基础，例如正在进行的围产期相关大脑可塑性的中断。另一种较少被探索的假说是，母亲持续的免疫激活和慢性低度炎症可能是产后情绪障碍的基础，也可能增加子女在以后的生活中患上躯体和情感障碍的风险，特别是在面临长期严重的生活压力时(=二次打击)。有趣的是，慢性应激干扰了海马神经发生，并导致慢性低度炎症。重要的是，与上述免疫激活在情绪障碍发展中的详细作用一致，我们最近表明，反复预免疫(S.C.)诱导的免疫调节。母牛分枝杆菌是一种丰富的土壤腐生植物，具有免疫调节特性，使用母牛分枝杆菌热灭活制剂(国家模式培养物收藏11659)，能够预防应激诱导的焦虑、自发性结肠炎和葡聚糖硫酸钠诱导的结肠炎(一种炎症性肠病的小鼠模型)加重。因此，在这项建议中，我们的目标是确定交配前给予母牛分枝杆菌是否可以保护母鼠免受妊娠应激对行为、HPA轴、炎症反应和海马神经发生的有害影响。此外，我们将确定这是否也可以保护后代免受产前压力和/或成年后暴露于慢性心理社会压力的影响。综上所述，该项目将确定免疫调节方法是否可以保护母亲和她的后代免受随后怀孕期间慢性应激的后果。