title: Bisphenol-A impairs myelination potential during development in the hippocampus of the rat brain.
abstract: Myelin is the functional implication of oligodendrocytes (OLs), which is involved in insulation of axons and promoting rapid propagation of action potential in the brain. OLs are derived from oligodendrocyte progenitor cells (OPCs), which proliferate, differentiate, and migrate throughout the central nervous system. Defects in myelination process lead to the onset of several neurological and neurodegenerative disorders. Exposure to synthetic xenoestrogen bisphenol-A (BPA) causes cognitive dysfunction, impairs hippocampal neurogenesis, and causes onset of neurodevelopmental disorders. However, the effects of BPA on OPC proliferation, differentiation and myelination, and associated cellular and molecular mechanism(s) in the hippocampus of the rat brain are still largely unknown. We found that BPA significantly decreased bromodeoxyuridine (BrdU)-positive cell proliferation and number and size of oligospheres. We observed reduced co-localization of BrdU with myelination markers CNPase and platelet-derived growth factor receptor-α (PDGFR-α), suggesting impaired proliferation and differentiation of OPCs by BPA in culture. We studied the effects of BPA exposure during prenatal and postnatal periods on cellular and molecular alteration(s) in the myelination process in the hippocampus region of the rat brain at postnatal day 21 and 90. BPA exposure both in vitro and in vivo altered proliferation and differentiation potential of OPCs and decreased the expression of genes and levels of proteins that are involved in myelination. Ultrastructural electron microscopy analysis revealed that BPA exposure caused decompaction of myelinated axons and altered g-ratio at both the developmental periods as compared to control. These results suggest that BPA exposure both during prenatal and postnatal periods alters myelination in the hippocampus of the rat brain leading to cognitive deficits.
authors.affiliation: Developmental Toxicology Division, Systems Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), 80 MG Marg, Lucknow, UP, 226001, India.
authors.forename: Shashi Kant
authors.initials: SK
authors.lastname: Tiwari
authors.forename: Swati
authors.initials: S
authors.lastname: Agarwal
authors.forename: Lalit Kumar Singh
authors.initials: LK
authors.lastname: Chauhan
authors.forename: Vijay Nath
authors.initials: VN
authors.lastname: Mishra
authors.forename: Rajnish Kumar
authors.initials: RK
authors.lastname: Chaturvedi
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
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