Murgatroyd Christopher A, Babb Jessica A, Bradburn Steven, Carini Lindsay M, Beamer Gillian L, Nephew Benjamin C
Centre for Healthcare Science Research, Manchester Metropolitan University, Manchester, UK.
Department of Anesthesia, Boston Children's Hospital, Boston, MA, USA.
Front Ecol Evol. 2016 Jan;3. doi: 10.3389/fevo.2015.00149. Epub 2016 Jan 12.
A social signal transduction theory of depression has been proposed that states that exposure to social adversity alters the immune response and these changes mediate symptoms of depression such as anhedonia and impairments in social behavior The exposure of maternal rats to the chronic social stress (CSS) of a male intruder depresses maternal care and impairs social behavior in the F1 and F2 offspring of these dams. The objective of the present study was to characterize basal peripheral levels of several immune factors and related hormone levels in the adult F2 offspring of CSS exposed dams and assess whether changes in these factors are associated with previously reported deficits in allogrooming behavior. CSS decreased acid glycoprotein (α1AGP) and intercellular adhesion molecule-1 (ICAM-1) in F2 females, and increased granulocyte macrophage-colony stimulating factor (GM-CSF) in F2 males. There were also sex dependent changes in IL-18, tissue inhibitors of metalloproteinases 1 (TIMP-1), and vascular endothelial growth factor (VEGF). Progesterone was decreased and alpha melanocyte stimulating hormone (α-MSH) was increased in F2 males, and brain-derived neurotrophic factor (BDNF) was decreased in F2 females. Changes in α1AGP, GM-CSF, progesterone, and α-MSH were correlated with decreased allogrooming in the F2 offspring of stressed dams. These results support the hypothesis that transgenerational social stress affects both the immune system and social behavior, and also support previous studies on the adverse effects of early life stress on immune functioning and stress associated immunological disorders, including the increasing prevalence of asthma. The immune system may represent an important transgenerational etiological factor in disorders which involve social and/or early life stress associated changes in social behavior, such as depression, anxiety, and autism, as well as comorbid immune disorders. Future studies involving immune and/or endocrine assessments and manipulations will address specific questions of function and causation, and may identify novel preventative measures and treatments for the growing number of immune mediated disorders.
一种关于抑郁症的社会信号转导理论被提出，该理论认为暴露于社会逆境会改变免疫反应，而这些变化介导了抑郁症的症状，如快感缺失和社交行为受损。将母鼠暴露于雄性入侵者的慢性社会应激（CSS）中，会抑制母性关怀，并损害这些母鼠F1和F2代后代的社交行为。本研究的目的是表征暴露于CSS的母鼠成年F2代后代中几种免疫因子的基础外周水平和相关激素水平，并评估这些因子的变化是否与先前报道的互舐行为缺陷有关。CSS降低了F2代雌性中的酸性糖蛋白（α1AGP）和细胞间粘附分子-1（ICAM-1），并增加了F2代雄性中的粒细胞巨噬细胞集落刺激因子（GM-CSF）。白细胞介素-18、金属蛋白酶组织抑制剂1（TIMP-1）和血管内皮生长因子（VEGF）也存在性别依赖性变化。F2代雄性中的孕酮降低，α-黑素细胞刺激素（α-MSH）增加，F2代雌性中的脑源性神经营养因子（BDNF）降低。α1AGP、GM-CSF、孕酮和α-MSH的变化与应激母鼠F2代后代互舐行为的减少相关。这些结果支持了代际社会应激影响免疫系统和社交行为的假设，也支持了先前关于早期生活应激对免疫功能和与应激相关的免疫疾病（包括哮喘患病率上升）的不利影响的研究。免疫系统可能是涉及社会和/或早期生活应激相关社交行为变化的疾病（如抑郁症、焦虑症和自闭症以及共病免疫疾病）中的一个重要代际病因因素。未来涉及免疫和/或内分泌评估及操作的研究将解决功能和因果关系的具体问题，并可能为越来越多的免疫介导疾病确定新的预防措施和治疗方法。
