Developmental Neurotoxicity: Some Old and New Issues

Abstract

The developing central nervous system is often more vulnerable to injury than the adult one. Of the almost 200 chemicals known to be neurotoxic, many are developmental neurotoxicants. Exposure to these compoundsin uteroor during childhood can contribute to a variety of neurodevelopmental and neurological disorders. Two established developmental neurotoxicants, methylmercury and lead, and two classes of chemicals, the polybrominated diphenyl ether flame retardants and the organophosphorus insecticides, which are emerging as potential developmental neurotoxicants, are discussed in this paper. Developmental neurotoxicants may also cause silent damage, which would manifest itself only as the individual ages, and may contribute to neurodegenerative diseases such as Parkinson’s or Alzheimer’s diseases. Guidelines for developmental neurotoxicity testing have been implemented, but there is still room for their improvement and for searching and validating alternative testing approaches.

The protective effect of Nigella Sativa oil extract against neurotoxicity induced by Valproic acid

“…Thus, most morphological changes such as neuronopathy (a loss of neurons), axonopathy (a degeneration of the neuronalaxon), myelinopathy (a loss of the glial cells surrounding the axon), or other gliopathies, would be considered adverse, even if structural and/or functional changes were mild or transitory. In addition, neurochemical changes, also in the absence of structural damage, should also be considered adverse, even if they are transient and reversible, as they bring about dysfunction (Giordano and Costa, 2012). Neurotoxicity can also happen as a result of indirect effects, such as harm to hepatic or cardiovascular structures, or because of interference with the endocrine systems.…”

Comparability of behavioural assays using zebrafish larvae to assess neurotoxicity

“…Exposure to neurotoxic substances may occur within the private home environment, in agricultural or industrial areas, or via the uptake of polluted food or drinking water (ArlienSøborg and Simonsen 2011). Neurotoxicity is also a known side effect of medical treatments such as chemotherapy and can occur as an indirect effect of cardiovascular or endocrine system dysfunction (Giordano and Costa 2012). Testing for neurotoxicity is becoming more and more relevant due to the increasing exposure to environmental contaminants, as well as the increasing number of people with neurological disorders.…”

“…In the early developing organism, neurotransmitters also influence cell proliferation, survival, and differentiation. Therefore, alterations in neurotransmitter levels which might be reversible in adults can cause permanent defects during the early development of an organism (Giordano and Costa 2012). Several neurodevelopmental diseases such as autism spectrum disorder have been associated with chemical exposures during early development (Lyall et al 2014).…”

Fingerprinting of neurotoxic compounds using a mouse embryonic stem cell dual luminescence reporter assay

“…Major limitations of presently available studies on neurotoxicity, both developmental and general, include the following aspects:

Relatively few clinical and epidemiological data are available (Smirnova et al 2014). Well-accepted exceptions are tragic events such as the large-scale methylmercury poisoning in Minamata (Ekino et al 2007) or the identification of the fetal valproate syndrome because of the widespread treatment of pregnant epileptic patients with valproic acid (Ozkan et al 2011; Smith and Whitehall 2009);

Neurotoxicity is typically not characterized by cytotoxicity (i.e., neuronal cell death), but rather by impact of toxicants on connectivity, structure, and function of the nervous system during development or at maturity (Giordano and Costa 2012);Extrapolation of data from animal experiments to the human situation may be challenging due to interspecies differences (“humans are no 70 kg mice” (Leist and Hartung 2013);In vitro studies on neurotoxicity usually use transformed or cancer cell lines, which have a response pattern significantly different from normal cells (Kadereit et al 2012; Stiegler et al 2011). …”