Postnatal Neuro-Behavioral Effects of Prenatal Ethanol Exposure in a Mouse Model
- Author(s): Kozanian, Olga Olia
- Advisor(s): Huffman, Kelly
- et al.
Alcohol consumption during pregnancy can produce developmental abnormalities in offspring brain and behavior that often persist into adulthood, resulting in lifelong neurobehavioral anomalies. Fetal alcohol spectrum disorders, or FASD, is an umbrella term that describes a range of adverse developmental conditions caused by prenatal alcohol, or ethanol exposure (PrEE), with epidemiological studies recently reporting up to 5% of children being diagnosed with some form of FASD. PrEE can manifest in a host of physical, cognitive, emotional and behavioral impairments, arising from underlying neurobiological damage in various brain regions, including the neocortex. In order to study the affects of PrEE on brain biology and behavior, our laboratory created a CD-1 mouse model of FASD, implementing a maternal voluntary consumption of 25% ethanol solution paradigm throughout gestation. In preliminary studies, our laboratory was first to demonstrate disrupted targeting of ipsilateral intraneocortical connections (INCs) within sensori-motor regions of neocortex, altered gene expression patterns, coupled with altered cortical thickness and subcortical anatomy in newborn PrEE mice and abnormal behavior in older PrEE mice (El Shawa et al., 2013; Abbott et al., 2016). Chapter one of this dissertation extends initial studies investigating structural differences between newborn PrEE and control mice by examining the long-term effects of PrEE on brain anatomy throughout development, in weanling and early adult PrEE mice, with results revealing long-term alterations in cortical anatomy and abnormal subcortical development from the in utero ethanol exposure. Furthermore, we examine and discuss behavioral implications of PrEE-induced cortical and subcortical damage in young adult mice. In chapter two, we investigate whether aberrant INCs and altered gene expression patterns found in the PrEE newborn are transient or persist into prepubescence. Here, we discuss the maintenance of PrEE-induced changes in gene expression and altered behavior through prepubescence, albeit recovery of ectopic cortical connectivity observed at birth. Finally, chapter three evaluates the impact of PrEE on components of brain and behavior involved in fear learning and memory recall. Specifically, we assess the long-term effects of early ethanol exposure on a Pavlovian fear-conditioning paradigm, with results indicating that PrEE significantly alters learning and memory of aversive stimuli in adulthood when conditioned earlier in development. In addition, we review the outcome of PrEE on brain regions involved in fear learning and emotion regulation in adulthood.
Further identification of the biological and behavioral phenotypes resulting from PrEE in this dissertation will contribute greatly toward discerning solutions in minimizing the severity and/or ameliorating ethanol-induced neurobehavioral damage.