Title:
Integrative approach to developmental neurotoxicity induced by low-dose perinatal exposure to industrial chemicals

 

Speaker:
Chiharu Tohyama
Emeritus Professor, The University of Tokyo; Visiting Professor, Faculty of Medicine, University of Tsukuba, and Chief, Health Environment, Science and Technology International Consulting (HESTIC).
E-mail: tohyamac-tky@umin.org
HP: http://www.hestic.com/

 

Abstract:
Devastating damage to the developing brain by excessive exposure to industrial chemicals have been evidenced by the history of environmental disorders, which represents an extreme end of the spectrum of neurodevelopmental disease phenotypes. In contrast, a current concern is that early life exposure to relatively low level of industrial chemicals does not induce overt signs and symptoms in dams or offspring, but may induce cognitive and behavioral abnormalities later in life. To protect the developing brain from chemical exposure, risk assessment of developmental neurotoxicity (DNT) should be appropriately performed as a precautious measure not to overlook the early signs and symptoms.
In our previous studies, perinatal exposure to a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced abnormal behavior as well as cognitive and behavioral abnormalities in rodent models. Our behavioral test data on higher brain function using an IntelliCage system were found to be reliable in terms of reproducibility. Our micro-morphologic analysis of TCDD-exposed brain supports the notion that the abnormal signs, such as dendrite length, complexity and spine density occur during gestation, and may underlie the cause of the abnormal phenotypes of cognitive and abnormal phenotypes later in life. It should be pointed out that routine histology according to the OECD DNT test guideline, TG426, cannot be sensitive enough to demonstrate such observations. Besides, in vitro tests that are conceived for alternatives to in vivo tests, are not able to reflect the complex nature of the central nervous system. Introduction of a research-oriented integrative approach, using both in vivo behavioral tests and micro-histological and molecular/biochemical analyses, to DNT test guidelines should be considered.

 

References:
Endo T et al., PLoS One, 7(12):e50741, 2012; Kakeyama M et al., Arch Toxicol. 88(3):789-98, 2014; Kimura E et al., Neurotoxicol Teratol, 52(Pt A):42-50, 2015; Kimura E et al., Biochem Biophys Res Commun, 22;476(2):108-13, 2016; Tohyama C, J Toxicol Sci. 41(Special):SP69-SP79, 2016; Aung KH et al., Front Neurosci,10:137, 2016; Kimura E et al., PLoS, 12(8):e0183497, 2017