Bisphenol-A suppresses neurite extension due to inhibition of phosphorylation of mitogen-activated protein kinase in PC12 cells

Abstract

An endocrine disrupter, bisphenol-A is widely used in t he product ion of plast ics and coating s. Recent ly, it was reported that bisphenol-A affected neurotransmitters in the mammalian brain. On t he basis of these reports, it was considered that bisphenol-A affected neuronal different iat ion. In t his study, the morphological changes in nerve growth factor (NFG)-induced different iat ion caused by bisphenol-A were confir med using a PC12 cell system. When a low concentrat ion of bisphenol-A was added to medium containing NGF, it inhibit ed neurit e extension. In addit ion, to clarify whether bisphenol-A affects the early and late stages of the NGF-signaling pathway in cell different iat ion, changes of phosphorylat ion of MAP kinases and cAMP-response element binding protein (CREB) in PC12 cells treated with and wit hout BPA in medium containing NGF were invest igated using western blot analysis. As results, bisphenol-A significant ly inhibit ed phosphorylat ion of CREB and ERK1/2 MAPK.

Loss of Hippocampal Oligodendrocytes Contributes to the Deficit of Contextual Fear Learning in Adult Rats Experiencing Early Bisphenol A Exposure

“…In line with this, the expression of NF-200 was also reduced. These results may not be surprising because BPA has been long known to be capable of disrupting normal neuronal development and suppressing the outgrowth of neurites [21,54]. Thus, with the reduced number of axons to be myelinated, less amount of OLs/MBP may be sufficient to support axonal myelination in hippocampus resulting in relatively intact myelination of individual axons.…”

A Unique Pattern of Bisphenol A Effects on Nerve Growth Factor Gene Expression in Embryonic Mouse Hypothalamic Cell Line N-44

“…We previously showed that BPA decreased the Bdnf gene expression in embryonic hypothalamic cells and affected the BDNF-NTRK2 neurotrophin system (10). Seki et al (11) have found that BPA causes morphological changes in NGFinduced differentiation and inhibits neurite extension in a PC12 cell line. It has also been reported to induce changes in both dendritic and synaptic development in foetal hypothalamic cells (12).…”

Visualized Gene Network Reveals the Novel Target Transcripts Sox2 and Pax6 of Neuronal Development in Trans-Placental Exposure to Bisphenol A

“…In neuronal or neuronal-like cells, neuronal differentiation is decreased in pheochromocytoma PC12 cells in pre-exposure to BPA (0.1, 1, 10 or 100 nM) for one week, longer or a week followed by a week's withdrawal [33]. PC12 cells treated with 43.8 nM BPA for 5 days suppress neurite extension through inhibition of phosphorylation of mitogen-activated protein kinase [19]. Rats exposed to 10 or 100 nM BPA for 7 days increases both MAP2 (microtubule associated protein-2) and synapsin I-positive areas for neuronal development as well as synaptic densities in hypothalamic neurons and glias [18].…”

“…BPA also causes adverse effects on neuronal morphology and functions as to interrupting neuronal dendritic and synaptic development in cultures of fetal rat hypothalamus cells at 10 and 100 nM [18]. BPA suppresses neurite extension by inhibiting phosphorylation of mitogen activated protein kinase (MAPK) in rat pheochromocytoma PC12 cells differentiated neuronal-like cells [19]. Furthermore, perinatal exposure to BPA causes GABAergic disinhibition and dopaminergic enhancement that is related to abnormal cortical basolateral amygdala synaptic transmission and plasticity; this effect may be responsible for hyperactivity and attention deficit in BPA-rats [20].…”