The environmental neurotoxicant PCB 95 promotes synaptogenesis via ryanodine receptor-dependent miR132 upregulation
| العنوان: | The environmental neurotoxicant PCB 95 promotes synaptogenesis via ryanodine receptor-dependent miR132 upregulation |
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| المؤلفون: | Mingyan Zhu, Gary A. Wayman, Adam Lesiak, Suzanne M. Appleyard, Hao Chen, Pamela J. Lein, Soren Impey |
| المصدر: | The Journal of neuroscience : the official journal of the Society for Neuroscience, vol 34, iss 3 Lesiak, Adam; Zhu, Mingyan; Chen, Hao; Appleyard, Suzanne M; Impey, Soren; Lein, Pamela J; et al.(2014). The environmental neurotoxicant PCB 95 promotes synaptogenesis via ryanodine receptor-dependent miR132 upregulation.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 34(3), 717-725. doi: 10.1523/JNEUROSCI.2884-13.2014. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/9gr02062 |
| بيانات النشر: | eScholarship, University of California, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Dendritic spine, polychlorinated biphenyls, Cells, Neurogenesis, Synaptogenesis, Hippocampal formation, CREB, Hippocampus, Medical and Health Sciences, Rats, Sprague-Dawley, Organ Culture Techniques, Downregulation and upregulation, Internal medicine, medicine, Animals, Cells, Cultured, Cultured, synaptogenesis, Neurology & Neurosurgery, biology, microRNA, Ryanodine receptor, General Neuroscience, Psychology and Cognitive Sciences, Neurosciences, Excitatory Postsynaptic Potentials, Ryanodine Receptor Calcium Release Channel, Articles, dendritic spines, musculoskeletal system, Polychlorinated Biphenyls, Spine, Coculture Techniques, Rats, Brain Disorders, MicroRNAs, Endocrinology, Mental Health, Synapses, Excitatory postsynaptic potential, biology.protein, Environmental Pollutants, Female, developmental neurotoxicity, Sprague-Dawley |
| الوصف: | Non–dioxin-like (NDL) polychlorinated biphenyls (PCBs) are widespread environmental contaminants linked to neuropsychological dysfunction in children. NDL PCBs increase spontaneous Ca2+oscillations in neurons by stabilizing ryanodine receptor (RyR) calcium release channels in the open configuration, which results in CREB-dependent dendritic outgrowth. In this study, we address the question of whether activation of CREB by NDL PCBs also triggers dendritic spine formation. Nanomolar concentrations of PCB 95, a NDL congener with potent RyR activity, significantly increased spine density and the frequency of miniature EPSCs in primary dissociated rat hippocampal cultures coincident with upregulation of miR132. Inhibition of RyR, CREB, or miR132 as well as expression of a mutant p250GAP cDNA construct that is not suppressed by miR132 blocked PCB 95 effects on spines and miniature EPSCs. PCB 95 also induced spine formation via RyR- and miR132-dependent mechanisms in hippocampal slice cultures. These data demonstrate a novel mechanism of PCB developmental neurotoxicity whereby RyR sensitization modulates spine formation and synaptogenesis via CREB-mediated miR132 upregulation, which in turn suppresses the translation of p250GAP, a negative regulator of synaptogenesis. In light of recent evidence implicating miR132 dysregulation in Rett syndrome and schizophrenia, these findings identify NDL PCBs as potential environmental risk factors for neurodevelopmental disorders. |
| وصف الملف: | application/pdf |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f823ed2e501fdf990722d15d778c42c https://escholarship.org/uc/item/9gr02062 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0f823ed2e501fdf990722d15d778c42c |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |