title: Perinatal exposure to bisphenol-A impairs spatial memory through upregulation of neurexin1 and neuroligin3 expression in male mouse brain.
abstract: Bisphenol-A (BPA), a well known endocrine disruptor, impairs learning and memory in rodents. However, the underlying molecular mechanism of BPA induced impairment in learning and memory is not well known. As synaptic plasticity is the cellular basis of memory, the present study investigated the effect of perinatal exposure to BPA on the expression of synaptic proteins neurexin1 (Nrxn1) and neuroligin3 (Nlgn3), dendritic spine density and spatial memory in postnatal male mice. The pregnant mice were orally administered BPA (50 µg/kgbw/d) from gestation day (GD) 7 to postnatal day (PND) 21 and sesame oil was used as a vehicle control. In Morris water maze (MWM) test, BPA extended the escape latency time to locate the hidden platform in 8 weeks male mice. RT-PCR and Immunoblotting results showed significant upregulation of Nrxn1 and Nlgn3 expression in both cerebral cortex and hippocampus of 3 and 8 weeks male mice. This was further substantiated by in-situ hybridization and immunofluorescence techniques. BPA also significantly increased the density of dendritic spines in both regions, as analyzed by rapid Golgi staining. Thus our data suggest that perinatal exposure to BPA impairs spatial memory through upregulation of expression of synaptic proteins Nrxn1 and Nlgn3 and increased dendritic spine density in cerebral cortex and hippocampus of postnatal male mice.
authors.affiliation: Biochemistry and Molecular Biology Laboratory, Brain Research Centre, Department of Zoology, Banaras Hindu University, Varanasi, India.
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Biochemistry and Molecular Biology Laboratory, Brain Research Centre, Department of Zoology, Banaras Hindu University, Varanasi, India.
authors.forename: Mahendra Kumar
authors.initials: MK
authors.lastname: Thakur
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis* / Q000235:genetics; D002540:Cerebral Cortex / Q000187:drug effects; D049229:Dendritic Spines / Q000187:drug effects / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000235:genetics; D010636:Phenols / Q000008:administration & dosage; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000473:pathology; D065852:Spatial Memory / Q000187:drug effects*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D010636:Phenols; C527193:Nrxn1 protein, mouse; C098004:neuroligin 3; C006780:bisphenol A; D000098826:Bisphenol A Compounds