Graduation Date

Spring 2022

Document Type

Thesis

Program

Master of Arts degree with a major in Psychology, option Academic Research

Committee Chair Name

Dr. Ethan Gahtan

Committee Chair Affiliation

HSU Faculty or Staff

Second Committee Member Name

Dr. Amanda Hanh

Second Committee Member Affiliation

HSU Faculty or Staff

Third Committee Member Name

Dr. Christopher Aberson

Third Committee Member Affiliation

HSU Faculty or Staff

Keywords

KCC2, Zebrafish, slc12a5, Bisphenol-A, Locomotor activity, CYP19a1b

Abstract

Bisphenol A (BPA), a manufactured compound found in consumer products, is known to adversely affect early brain development by disrupting normal estrogen signaling. Recently, BPA was reported to suppress expression of a gene encoding the neuron-specific chloride ion transporter, KCC2. Human and animal studies show suppressing KCC2 can cause neuronal and behavioral hyperactivity. Therefore, some adverse effects of BPA may be due to KCC2 suppression and consequent neuronal hyperactivity. This study aimed to determine whether BPA exposure during brain development alters KCC2 expression. A secondary purpose was to evaluate whether a new transgenic zebrafish line, KCC2:mCitrine,could be used to track changes in KCC2 expression in vivo by fluorescence imaging. Zebrafish embryos treated with 2.5µM BPA during days 0-5 post-fertilization were tested for (1) KCC2:mCitrine fluorescence brightness; (2) KCC2 gene expression using RT qPCR as an external validation for fluorescence; (3) Behavioral activity level, and; (4) estrogen signaling, as a BPA manipulation check. Results showed that BPA produced expected estrogenic effects in the developing brain and decreased KCC2 expression at specific developmental time points. However, BPA did not produce expected behavioral hyperactivity. Lastly, RT-qPCR data were uninterpretable so fluorescence brightness could not be externally validated as a measure of gene expression. This pattern of results supports the conclusion that estrogenic effects of BPA can suppress KCC2 expression in developing zebrafish brains, consistent with previous research implicating BPA as a teratogen, and KCC2 expression as a mechanism -- and potential treatment target -- in human developmental disorders.

Citation Style

APA

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