Chapter 63 - Cell signaling mechanisms in developmental neurotoxicity

Abstract

This chapter describes key cell signaling mechanisms by which neurotoxic chemicals inflict damage on or induce neurotoxicity to the developing nervous system. The major mechanisms in cell signaling cascades by which neurotoxicants alter neural cell developmental processes during early life exposure are discussed in this chapter. It is important to note that many industrial chemicals, pesticides and heavy metals are capable of inducing neurotoxicity in the human central nervous system, particularly in developing brains. It also summarizes key cell signaling mechanisms by which neurotoxic chemicals inflict damage or induce neurotoxicity to the developing nervous system. A growing body of evidence suggests that exposure of developing neural cells to neurotoxic chemicals leads to depolarization of cell membranes, destruction of cell architecture proteins, mitochondrial dysfunction and induction of oxidative stress, DNA damage and effects on DNA synthesis, lasting changes in gene expression, modification of key signaling proteins in various pathways, epigenetic changes, and so on. Several industrial chemicals, including some metals (e.g., lead, methylmercury), polychlorinated biphenyls, arsenic and toluene, induce subclinical brain dysfunctions and neurodevelopmental disorders. Exposure to these chemicals during early fetal development can cause brain injury at doses much lower than doses that affect adult brain functions. It explains cell signaling mechanisms in developmental neurotoxicity. Glial cells and neurons in the nervous system are post-mitotic cells and are particularly sensitive to the ROS, which cause neuronal damage. It also covers impacts on DNA synthesis, gene expression deregulation, protein modification, epigenetic modifications, and cell signaling integration.