Decoding the language of epigenetics during neural development is key for understanding development as well as developmental neurotoxicity.

Published

Journal Article

Neural development is a delicate process that can be disrupted by pollution that exerts detrimental impact on neural signaling. This commentary highlights recent discoveries in the arena of research at the interface of environmental toxicology and developmental neuroscience relating to toxicity mechanisms of bisphenol A (BPA), a ubiquitous chemical used in manufacturing of plastics and epoxy resins that is known to bind to and interfere with estrogen receptors, estrogen-receptor-related receptors and other receptors for gonadal steroids. It was recently observed that BPA disrupts the perinatal chloride shift, a key neurodevelopmental mechanism that brings down neuronal chloride from ~100 mM to ~20 mM within weeks. The chloride shift happens in all central nervous systems of vertebrates around parturition. High neuronal chloride supports neuron precursors' migrations, low neuronal chloride is the prerequisite for inhibitory action of neurotransmitters GABA and glycine, and thus an absolute requisite for normal functioning of the mature CNS. One critical contributor to the neuronal chloride shift is the concomitant upregulation of expression of the chloride-extruding transporter molecule, KCC2. We highlight recent findings including our discovery that BPA disrupts the chloride shift in a sex-specific manner by recruiting epigenetics mechanisms. These could be relevant for childhood neuropsychiatric disorders as well as for liability to develop chronic neuropsychiatric diseases later in life.

Full Text

Duke Authors

Cited Authors

  • Yeo, M; Patisaul, H; Liedtke, W

Published Date

  • November 2013

Published In

Volume / Issue

  • 8 / 11

Start / End Page

  • 1128 - 1132

PubMed ID

  • 24071811

Pubmed Central ID

  • 24071811

Electronic International Standard Serial Number (EISSN)

  • 1559-2308

Digital Object Identifier (DOI)

  • 10.4161/epi.26406

Language

  • eng

Conference Location

  • United States