title: Loss of Hippocampal Oligodendrocytes Contributes to the Deficit of Contextual Fear Learning in Adult Rats Experiencing Early Bisphenol A Exposure.
abstract: During early development, continuous exposure to environmental contaminants such as bisphenol A (BPA) is known to alter neuronal development, resulting in aberrant brain structure and predisposing individuals to developing neuropsychiatric disorders later in life. While the altered oligodendrocyte (OL) structure and function have been casually linked to the occurrence of numerous psychiatric diseases, it remains open whether early BPA exposure (EBE) also recruits OLs to mediate its toxicity in the brain. Here, we observed that EBE from birth to postnatal day 21 caused a substantial loss of hippocampal OLs in rat pups. The OL loss was enduring and manifested even when the affected pups spanned into their adulthood. In parallel, the expression of two key proteins in mature OLs, myelin basic protein (MBP), and monocarboxylate transporter 1 (MCT1) was markedly downregulated in adult hippocampus with a considerable reduction in the number of myelinated axons. By contrast, the myelination of individual axons remained intact. The altered hippocampal OLs were related to EBE-mediated disruption of estrogen receptor (ER) signaling in developing OLs and could be readily prevented by treatment with low level of ICI 182780, an ER antagonist. Importantly, the adult rats subject to EBE exhibited clear deficit in contextual fear memory, which highly correlated with OL loss and decreased MBP and MCT1 expression in hippocampus. The OL loss may thus represent an alternative route through which EBE has its adversity on the brain and contributes to the development of neuropsychiatric illness.
authors.affiliation: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang, 310031, China. xuxiaobin70@hotmail.com.
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Xu
authors.affiliation: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang, 310031, China.
authors.forename: Shi-Jun
authors.initials: SJ
authors.lastname: Fan
authors.affiliation: Center for Basic Medical Experiment, Nanchang University, Nanchang, 310031, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: He
authors.affiliation: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang, 310031, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ke
authors.affiliation: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang, 310031, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Song
authors.affiliation: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang, 310031, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang, 310031, China.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Zhang
authors.affiliation: School of Life Science, Nanchang University, Nanchang, 310031, China.
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Department of Neurology, the 2nd Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Yin
authors.affiliation: Medical Institute of Developmental Disorders Research, Showa University, 6-11-11 Kita-Karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Kato
authors.affiliation: Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang, 310031, China. panbingxing@ncu.edu.cn.|Department of Neurology, the 2nd Affiliated Hospital of Nanchang University, Nanchang, 330006, China. panbingxing@ncu.edu.cn.
authors.forename: Bing-Xing
authors.initials: BX
authors.lastname: Pan
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002452:Cell Count; D004781:Environmental Exposure; D005239:Fear; D005260:Female; D006624:Hippocampus / Q000473:pathology* / Q000648:ultrastructure; D007858:Learning; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D004676:Myelin Basic Protein; D009186:Myelin Sheath / Q000378:metabolism; D009836:Oligodendroglia / Q000473:pathology*; D010636:Phenols / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D027981:Symporters / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D027501:Monocarboxylic Acid Transporters; D004676:Myelin Basic Protein; D010636:Phenols; D011960:Receptors, Estrogen; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Estrogen receptor; Fear memory; Hippocampus; Oligodendrocytes