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Journal article
Mice exposed to bisphenol A exhibit depressive-like behavior with neurotransmitter and neuroactive steroid dysfunction
Hormones and behavior, v 102
01 Jun 2018
PMID: 29763587
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Fetal exposure to endocrine disrupting chemicals (EDCs) has been associated with adverse neurobehavioral outcomes across the lifespan and can persist across multiple generations of offspring. However, the underlying mechanisms driving these changes are not well understood. We investigated the molecular perturbations associated with EDC-induced behavioral changes in first (F1) and second (F2) filial generations, using the model EDC bisphenol A (BPA). C57BL/6J dams were exposed to BPA from preconception until lactation through the diet at doses (10 mu g/kg bw/d-lower dose or 10 mg/kg bw/d-upper dose) representative of human exposure levels. As adults, F1 male offspring exhibited increased depressive-like behavior, measured by the forced swim test, while females were unaffected. These behavioral changes were limited to the F1 generation and were not associated with altered maternal care. Transcriptome analysis by RNA-sequencing in F1 control and upper dose BPA-exposed adult male hippocampus revealed neurotransmitter systems as major pathways disrupted by developmental BPA exposure. High performance liquid chromatography demonstrated a male-specific reduction in hippocampal serotonin. Administration of the selective serotonin reuptake inhibitor fluoxetine (20 mg/kg bw) rescued the depressive-like phenotype in males exposed to lower, but not upper, dose BPA, suggesting distinct mechanisms of action for each exposure dose. Finally, high resolution mass spectrometry revealed reduced circulating levels of the neuroactive steroid dehydroepiandrosterone in BPA-exposed males, suggesting another potential mechanism underlying the depressive-like phenotype. Thus, behavioral changes associated with early life BPA exposure may be mediated by sex-specific disruptions in the serotonergic system and/or sex steroid biogenesis in male offspring.
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Details
- Title
- Mice exposed to bisphenol A exhibit depressive-like behavior with neurotransmitter and neuroactive steroid dysfunction
- Creators
- Frances Xin - University of PennsylvaniaErin Fischer - University of PennsylvaniaChristopher Krapp - University of PennsylvaniaElizabeth N. Krizman - Children's Hospital of PhiladelphiaYemin Lan - University of PennsylvaniaClementina Mesaros - University of PennsylvaniaNathaniel W. Snyder - Drexel UniversityAmita Bansal - Children's Hospital of PhiladelphiaMichael B. Robinson - Children's Hospital of PhiladelphiaRebecca A. Simmons - Children's Hospital of PhiladelphiaMarisa S. Bartolomei - University of Pennsylvania
- Publication Details
- Hormones and behavior, v 102
- Publisher
- Elsevier
- Number of pages
- 12
- Grant note
- March of Dimes U54 HD086984 / University of Pennsylvania Neurobehavior Testing Core ES023284; ES013508 / NIEHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) U54HD086984 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) R01DK114054 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) T32ES019851 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000437553000011
- Scopus ID
- 2-s2.0-85047056399
- Other Identifier
- 991019167977304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Behavioral Sciences
- Endocrinology & Metabolism