Examining the impact of neuroimmune dysregulation on social behavior of male and female juvenile rats
Date
2020
Authors
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Publisher
University of Delaware
Abstract
Many neurodevelopmental disorders are associated with altered social behavior. While it is common to try to examine these disorders with syndrome-specific animal models, it is also advantageous to consider them in terms of functional dimensions (e.g., social behavior), rather than by diagnostic labels. Thus, we may be able to move away from diagnostic labels that are often comorbid and heterogeneous and toward a diagnostic and therapeutic system that can help more people. Epidemiological data indicate that environmental factors contribute to the risk for subsequent neurodevelopmental disorders, including those with aberrant social behavior. Early-life exposure to infectious pathogens is one of those environmental factors, suggesting that activation of the immune system during early development may contribute to disease pathology. In the current project, we examined the impact of neonatal infection, with or without juvenile immune activation, on the expression of social behavior in male and female juvenile rats. Moreover, we examined how these immune activations impacted the expression of inflammatory cytokines and important microglial signaling molecules in the juvenile 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. According to the two-hit hypothesis of neuroinflammation, increases in inflammatory cytokines and chemokines and changes in behavior should be most robust in rats that are exposed to both early-life and later-life immune activation. In the current project, this was sometimes true; however, neonatal infection alone and juvenile LPS treatment alone also significantly increased the expression of important immune molecules within the juvenile brain and impacted social behavior. Taken together, these behavioral and molecular data support the sensitivity of the juvenile brain to immune activation (both with and without neonatal infection), particularly in the expression of age-dependent social behavior. Thus, environmental factors that activate the immune system during juvenile development, either with or without perinatal immune activation, may also be significant risk factors for children diagnosed with developmental disorders that manifest with aberrant social behavior. These data warrant the design of additional studies that will help to develop novel (and modify existing) therapeutic targets or preventative measures to help those who exhibit severely disordered social behavior, and accordingly, a life disabled.
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Keywords
Neurodevelopment, Neuroinflammation, Social behavior