Many individuals diagnosed with neuropsychiatric disorders, such as autism, attention-deficit/hyperactivity disorder, schizophrenia, and social anxiety disorder, all share a common dimension of aberrant social behavior. Epidemiological data indicate that adverse environmental factors contribute to the risk for neurodevelopmental disorders, including those associated with aberrant social behavior. Early-life exposure to infectious pathogens is one of those adverse environmental factors, suggesting that activation of the immune system during early development may contribute to disease pathology associated with altered social behavior. In the current project, we examined the impact of neonatal infection, with or without juvenile immune activation, on the expression of juvenile social behavior and on the expression of inflammatory cytokines and microglial signaling molecules in the juvenile rat brain. The outcomes of these experiments revealed that neonatal infection significantly decreased juvenile social interaction, but significantly increased juvenile play behavior in male and female rats. Moreover, neonatal infection alone, juvenile immune activation alone, and neonatal infection plus juvenile immune activation all significantly impaired social recognition in juvenile male rats. Juvenile female rats (including controls) did not demonstrate social recognition as measured in our three-chamber social recognition test. Taken together, the behavioral and molecular data presented here support the sensitivity of the developing brain to immune activation, particularly in the expression of age-appropriate social behaviors. These data warrant the design of additional studies to examine the mechanistic relationship between early-life immune activation and aberrant social behavior to develop novel as well as modify existing therapeutic targets and preventative measures to help those who display aberrant social behavior.

许多被诊断患有神经精神疾病的人，例如自闭症、注意力缺陷/多动障碍、精神分裂症和社交焦虑症，都具有异常社交行为的共同维度。流行病学数据表明，不利的环境因素会增加神经发育障碍的风险，包括那些与异常社会行为相关的因素。生命早期接触传染性病原体是不利的环境因素之一，这表明在早期发育过程中免疫系统的激活可能导致与社会行为改变相关的疾病病理学。在当前的项目中，我们检查了新生儿感染的影响，无论是否激活青少年免疫，幼年社会行为的表达以及幼年大鼠脑中炎性细胞因子和小胶质细胞信号分子的表达。这些实验的结果表明，新生儿感染显着降低了青少年的社交互动，但显着增加了男性的青少年游戏行为和雌性老鼠。此外，单独的新生儿感染、单独的幼年免疫激活和新生儿感染加幼年免疫激活均显着损害幼年雄性大鼠的社会认知。在我们的三室社会认可测试中，幼年雌性大鼠（包括对照组）没有表现出社会认可。总之，这里提供的行为和分子数据支持发育中的大脑对免疫激活的敏感性，特别是在与年龄相适应的社会行为的表达方面。这些数据保证设计额外的研究来检查生命早期免疫激活和异常社会行为之间的机制关系，以开发新的以及修改现有的治疗目标和预防措施，以帮助那些表现出异常社会行为的人。