Bisphenol A (BPA) is one of the most prevalent manufactured chemicals in the world. An organic compound with estrogenic effects, it is used in the production of plastic composites and epoxy resins that are used to make food containers, dental products, thermal receipt paper, and many other items that we encounter on a daily basis. Because of its pervasive presence in our environment and ecosystem, it is critical that we understand the physiological effects of our incidental contact with BPA. The objective in this proposal is to focus on the mature central nervous system and identify the role of BPA on neural stem cells and neuronal development in the adult brain. One of the most striking examples of adult neural plasticity is the de novo formation of neurons throughout life in the dentate gyrus of the hippocampus. Convergent data suggests that this phenomenon plays a critical role in cognition and the regulation of affective behavior. Many of these functional roles appear to be part of a feedback loop in which environmental factors can alter the levels of adult neurogenesis, which in turn may alter our ability to cope with environmental demands. It is therefore paramount that one identifies the nature and mechanisms underlying the interaction between this form of adult neural plasticity and the environment. One such area in need of systematic investigation is the neural impact of frequently encountered environmental chemicals. To begin to address this gap in knowledge, the focus here is on BPA as an entry point for a rigorous analysis of how a near ubiquitous chemical contaminant may affect the activation and fate choice of neural stem cells and the development of their neuronal progeny. To accomplish this objective, novel quantitative approaches developed and refined in this laboratory will be used to analyze how BPA may regulate stem cell behavior and the properties of newborn neurons in the adult hippocampus. Taking advantage of a recently developed "clonal analysis" approach, both the identifying and quantifying properties of individual stem cells and stem cell populations in the adult brain following systemic exposure to BPA will be tested (Specific Aim 1). Further quantification of the impact of BPA on the developmental trajectory of newborn neurons will be accomplished using retroviral-mediated fluorescent labeling to enable morphological and electrophysiological analyses (Specific Aim 2). The results of these experiments should provide critical new information on the potential health risks of exposure to BPA and its effect on the adult central nervous system.

Public Health Relevance

BPA is one of the most prevalent chemicals in our environment but there are little data on its effect on the adult central nervous system. Our proposed experiments will provide critical new information regarding the effect of BPA on neural stem cells and development in the adult brain and provide a foundation for future regulatory evaluation of this chemical.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Exploratory/Developmental Grants (R21)
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Study Section
Special Emphasis Panel (ZES1-TN-D (ST))
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Reinlib, Leslie J
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Johns Hopkins University
Schools of Medicine
United States
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Felling, Ryan J; Song, Hongjun (2015) Epigenetic mechanisms of neuroplasticity and the implications for stroke recovery. Exp Neurol 268:37-45
Guo, Junjie U; Su, Yijing; Shin, Joo Heon et al. (2014) Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat Neurosci 17:215-22
Christian, Kimberly M; Song, Hongjun; Ming, Guo-li (2014) Functions and dysfunctions of adult hippocampal neurogenesis. Annu Rev Neurosci 37:243-62
Sun, Gerald J; Sailor, Kurt A; Mahmood, Qasim A et al. (2013) Seamless reconstruction of intact adult-born neurons by serial end-block imaging reveals complex axonal guidance and development in the adult hippocampus. J Neurosci 33:11400-11
Jang, Mi-Hyeon; Bonaguidi, Michael A; Kitabatake, Yasuji et al. (2013) Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis. Cell Stem Cell 12:215-23
Kaas, Garrett A; Zhong, Chun; Eason, Dawn E et al. (2013) TET1 controls CNS 5-methylcytosine hydroxylation, active DNA demethylation, gene transcription, and memory formation. Neuron 79:1086-93
Shin, Jaehoon; Ming, Guo-Li; Song, Hongjun (2013) By hook or by crook: multifaceted DNA-binding properties of MeCP2. Cell 152:940-2
Liu, Shuo; Wang, Jin; Su, Yijing et al. (2013) Quantitative assessment of Tet-induced oxidation products of 5-methylcytosine in cellular and tissue DNA. Nucleic Acids Res 41:6421-9
Berg, Daniel A; Belnoue, Laure; Song, Hongjun et al. (2013) Neurotransmitter-mediated control of neurogenesis in the adult vertebrate brain. Development 140:2548-61