title: Increased apoptosis and abnormal visual behavior by histone modifications with exposure to para-xylene in developing Xenopus.
abstract: Xylene and its derivatives are raw materials widely used in industry and known to be toxic to animals. However, the mechanism underlying the neurotoxicity of para-xylene (PX) to the central nervous system (CNS) in vivo is less clear. Here, we exposed Xenopus laevis tadpoles to sub-lethal concentrations of PX during the critical period of brain development to determine the effects of PX on Xenopus development and visual behavior. We found that the abnormality rate was significantly increased with exposure to increasing concentrations of PX. In particular, the number of apoptotic cells in the optic tectum was dramatically increased with exposure to PX at 2mM. Long-term PX exposure also resulted in significant deficits in visually guided avoidance behavior. Strikingly, co-incubation with PX and d-glucuronolactone (GA) decreased the number of apoptotic cells and rescued the avoidance behavior. Furthermore, we found that the acetylation of H4K12 (H4K12ac) and the dimethylation of H3K9 (H3K9me2) in the optic tectum were significantly increased in PX-treated animals, and these effects were suppressed by GA treatment. In particular, the increase in apoptotic cells in PX-treated brains was also inhibited by GA treatment. These effects indicate that epigenetic regulation plays a key role in PX-induced apoptosis and animal behavior. In an effort to characterize the neurotoxic effects of PX on brain development and behavior, these results suggest that the neurotoxicity of PX requires further evaluation regarding the safety of commercial and industrial uses.
authors.affiliation: Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Juanmei
authors.initials: J
authors.lastname: Gao
authors.affiliation: Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Hangze
authors.initials: H
authors.lastname: Ruan
authors.affiliation: Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Xianjie
authors.initials: X
authors.lastname: Qi
authors.affiliation: Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Guo
authors.affiliation: College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Jingna
authors.initials: J
authors.lastname: Zheng
authors.affiliation: College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.affiliation: College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Yanxiao
authors.initials: Y
authors.lastname: Fang
authors.affiliation: College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Minjiao
authors.initials: M
authors.lastname: Huang
authors.affiliation: College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Xu
authors.affiliation: Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China. Electronic address: shen@idrbio.org.
authors.forename: Wanhua
authors.initials: W
authors.lastname: Shen
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D002658:Developmental Disabilities / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D005965:Glucuronates / Q000494:pharmacology; D042421:Histone Code / Q000187:drug effects*; D006657:Histones / Q000187:drug effects / Q000378:metabolism; D008745:Methylation / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D013477:Superior Colliculi / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D014796:Visual Perception / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D014982:Xenopus laevis; D014992:Xylenes / Q000633:toxicity*
chemical_list: D005965:Glucuronates; D006657:Histones; D018696:Neuroprotective Agents; D014992:Xylenes; C004940:glucuronolactone; C031286:4-xylene
keywords: Xenopus; apoptosis; avoidance behavior; histone modification; optic tectum; para-xylene