Bisphenol A alters transcript levels of biomarker genes for Major Depressive Disorder
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1 II International Health Congress Gaia-Porto 19 th -21 st November 2015 Bisphenol A alters transcript levels of biomarker genes for Major Depressive Disorder Edna Ribeiro-Varandas *1,2, H. Sofia Pereira 2, Wanda Viegas 2 and Margarida Delgado 2 1 Lisbon School of Health Technology, Instituto Politécnico de Lisboa, Av. D. João II, Lote , Lisboa, Portugal 2 Landscape, Environment, Agriculture and Food (LEAF), Instituto Superior de Agronomia, Universidade de Lisboa, Tapada da Ajuda Lisboa, Portugal
2 INTRODUCTION: Bisphenol A Bisphenol A synthesised in 1891 Widespread production since Increased proliferation rate of MCF7 cells Fetuses shtml BPA as an endocrine disruptor chemical Erin K. Shanle and Wei Xu 2010
3 INTRODUCTION: Bisphenol A Worldwide risk assessment of BPA In vivo studies ERβ and GPR30 (Hippocampus and cortex) Cognitive function and neuronal structure Years or decades Synaptic remodeling (Hippocampus and prefrontal cortex) Adapted from Vandenberg L. et al 2009 Human epidemiological studies Childhood learning development and behavior problems Neuropsychiatric disorders (anxiety/depression)
4 INTRODUCTION: Major Depressive Disorder (MDD) MDD is a moderately heritable disorder characterized by one or more Major Depressive Episodes Laboratory tests to suport MDD diagnosis are not available Diagnosis and treatment are based on various signs and symptoms not always fitting into strict diagnostic categories Research for biological markers of neuropsychiatric disorders has been a challenge Biomarker genes for MDD diagnostics : PLSCR1 (phospholipid scramblase 1): Multiple cellular processes - DNA binding, calcium ion binding, epidermal growth factor receptor binding, protein binding CAPRIN1 (cell cycle associated protein 1): RNA binding PROK2 (Prokineticin 2): Component of the circadian clock ZBTB16 (zinc finger and BTB domain containing 16 ): Involved in cell cycle progression, and interacts with a histone deacetylase
5 METHODS: Cellular Models Vascular system Human Umbilical Vein Endothelial Cells Digestive tract system Human Colon Adenocarcinona Cells HUVEC HT29 BPA low-dose effects - Biological changes occurring in the concentration range of typical human exposures BPA exposure: 10ng/ml (44nM) (found in human biological samples in environmental exposure) 1μg/ml (4μM)(found in human biological samples in occupational exposure)
6 METHODS Cell cultures HT29 (RPMI) HUVEC (EGM-2) Cytological analysis Immunofluorescence DNA DAPI stain Transcriptional analysis RNA Extraction qrt-pcr
7 RESULTS: Characterization of Estrogen Receptors HUVEC and HT29 cell line - Negative for ERα - Positive for ERβ HUVEC - Negative for GPR30 in culture conditions ERβ HUVEC HT29 HT29 GPR30 Total protein levels DAPI GPR30 HT29 cell line endogenously express GPR30 receptor Ribeiro-Varandas E et al Bisphenol A at concentrations found in human serum induces aneugenic effects in endothelial cells. Mutation Research. 751: 27-33
8 Mean log2 fold change in relation to vehicle RESULTS: BPA transcriptional effects on MDD biomarkers HUVEC HT29 24 h BPA 10ng/ml 72 h BPA 1µg/ml 24 h BPA 10ng/ml 72 h BPA 1µg/ml Student s t test * p < 0.01 HUVEC: BPA induces more marked effects after prolonged exposures (72 h) to the higher BPA dose HT29: Stronger effects are detected after short exposure (24 h) to the lower assayed concentration Edna Ribeiro-Varandas, H Sofia Pereira, Wanda Viegas, Margarida Delgado. Bisphenol A alters transcript levels of biomarker genes for Major Depressive Disorder in Vascular Endothelial Cells and Colon Cancer Cells. Accepted in Chemosphere ID:CHEM36227.
9 CONCLUSION MDD biomarkers are differentially altered by BPA Importance of a better understanding of BPA cellular effects Substantiate increasing concerns that this xenoestrogen may have hazardous effects on human health Importance of BPA risk assessment
10 ACKNOWLEDGMENTS This work was funded by Fundação para a Ciência e Tecnologia (Portugal), PTDC/AACAMB/103968/2008, Pest- OE/AGR/UI0240/2014 and grant SFRH/BD/44277/2008 to E. Ribeiro-Varandas.
11 II International Health Congress Gaia-Porto 19 th -21 st November 2015 Bisphenol A alters transcript levels of biomarker genes for Major Depressive Disorder
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