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Intrauterine Inflammation affects Brain Development and Cognitive Behavior in a Sex-dependent Manner

Makinson, Ryan A
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1516718219342111

Abstract Details

2017, PhD, University of Cincinnati, Medicine: Neuroscience/Medical Science Scholars Interdisciplinary.
Intrauterine inflammation (IUI) is a prevalent health concern that impacts approximately 10-15% of births annually. This clinical condition is termed chorioamnionitis, and it is characterized by inflammation of the uterus and uterus-associated tissue along with the developing offspring. Despite the prevalence of chorioamnionitis, testing for IUI is not routinely monitored nor are treatment measures well-researched. In humans, chorioamnionitis is associated with a number of psychiatric and developmental disorders, such as cerebral palsy, learning disabilities, schizophrenia and attention-deficit/hyperactivity disorder. Exposure to brain inflammation during early life development is thought to be linked to abnormal behavioral or developmental phenotypes later in life, but the consequences of IUI on brain development remain poorly understood. The objective of this dissertation research is to better characterize the behavioral and neurological effects of IUI exposure. Chapter one will outline the interactions between the brain and the immune system, as well as introduce our model of IUI. Along with the role of microglia and myelinating cells, the behavioral impact of brain inflammation will also be discussed. Chapter two will investigate the hypothesis that IUI exposure negatively alters developmental programming of the immune system and establishment of brain myelination. Specifically, findings discussed will include assessment in the immune response to a “second-hit” acute immune stimulation and changes in the expression of genes and proteins linked to myelin synthesis and inflammation in both neonatal and adult mice. Chapters three and four will explore the effects of IUI exposure on cognition and behavior, as well as changes in gene expression in adult mice. Findings discussed will include modifications in responses to tests designed to assess generalized anxiety, motivation, working memory, locomotion, impulsive-like behaviors and changes in gene expression within the prefrontal cortex. We will also assess cognitive changes in animals following an acute immune stimulation. Chapter five will discuss the clinical and mechanistic implications of these findings within a broader context. In all chapters, sex differences to IUI exposure will be explored, due to the multifaceted role of estrogen on the immune system, brain development and behavior. Together, experiments presented support the overarching hypothesis that IUI greatly alters brain development and function in a sex-dependent manner, in part through interactions with microglia, as well as introduce novel concepts and approaches to study early life brain development.
Matia| Solomon, Ph.D. (Committee Chair)
James Herman, Ph.D. (Committee Member)
Teresa Reyes, Ph.D. (Committee Member)
Renu Sah, Ph.D. (Committee Member)
Kim Seroogy, Ph.D. (Committee Member)
204 p.
Neurology
Brain; Inflammation; Prefrontal Cortex; Cognition; Chorioamnionitis; Behavior

Recommended Citations

Citations

  • Makinson, R. A. (2017). Intrauterine Inflammation affects Brain Development and Cognitive Behavior in a Sex-dependent Manner [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1516718219342111

    APA Style (7th edition)

  • Makinson, Ryan. Intrauterine Inflammation affects Brain Development and Cognitive Behavior in a Sex-dependent Manner. 2017. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1516718219342111.

    MLA Style (8th edition)

  • Makinson, Ryan. "Intrauterine Inflammation affects Brain Development and Cognitive Behavior in a Sex-dependent Manner." Doctoral dissertation, University of Cincinnati, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1516718219342111

    Chicago Manual of Style (17th edition)

ucin1516718219342111
445
© 2017, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.