Gestational arsenic exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain

Several studies found that reduction of 5-hydroxymethylcytosine (5hmC), a marker of DNA hydroxymethylation highly enriched in developing brain, is associated with anxiety-like behaviors. This study aimed to investigate whether gestational arsenic (As) exposure induces anxiety-like behaviors in adult...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jin-Wei Lv, Ya-Ping Song, Zhi-Cheng Zhang, Yi-Jun Fan, Fei-Xiang Xu, Lan Gao, Xiao-Yi Zhang, Cheng Zhang, Hua Wang, De-Xiang Xu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Arsenic Brain development Anxiety-like behavior Ten-eleven translocation (TET) activity DNA hydroxymethylation Environmental pollution TD172-193.5 Environmental sciences GE1-350
Acceso en línea:	https://doaj.org/article/bcebdf6089234a74b6b8a37f26104355
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:bcebdf6089234a74b6b8a37f26104355
record_format	dspace
spelling	oai:doaj.org-article:bcebdf6089234a74b6b8a37f261043552021-11-06T04:16:03ZGestational arsenic exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain0147-651310.1016/j.ecoenv.2021.112901https://doaj.org/article/bcebdf6089234a74b6b8a37f261043552021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0147651321010137https://doaj.org/toc/0147-6513Several studies found that reduction of 5-hydroxymethylcytosine (5hmC), a marker of DNA hydroxymethylation highly enriched in developing brain, is associated with anxiety-like behaviors. This study aimed to investigate whether gestational arsenic (As) exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain. The dams drank ultrapure water containing NaAsO2 (15 mg/L) throughout pregnancy. Anxiety-like behaviors were evaluated and developing brain 5hmC was detected. Results showed that anxiety-like behaviors were observed in As-exposed adult offspring. In addition, 5hmC content was reduced in As-exposed fetal brain. Despite no difference on Tet1, Tet2 and Tet3 expression, TET activity was suppressed in As-exposed fetal brain. Mechanistically, alpha-ketoglutarate (α-KG), a cofactor for TET dioxygenases, was reduced and Idh2, a key enzymatic gene for mitochondrial α-KG synthesis, was downregulated in As-exposed fetal brain. Of interest, ascorbic acid, a cofactor for TET dioxygenases, reversed As-induced suppression of TET activity. Moreover, ascorbic acid attenuated As-induced reduction of 5hmC in fetal brain. In addition, ascorbic acid alleviated As-induced anxiety-like behaviors in adult offspring. Taken together, these results suggest that gestational As exposure induces anxiety-like behaviors in adult offspring, possibly at part, by inhibiting DNA hydroxymethylation in developing brain.Jin-Wei LvYa-Ping SongZhi-Cheng ZhangYi-Jun FanFei-Xiang XuLan GaoXiao-Yi ZhangCheng ZhangHua WangDe-Xiang XuElsevierarticleArsenicBrain developmentAnxiety-like behaviorTen-eleven translocation (TET) activityDNA hydroxymethylationEnvironmental pollutionTD172-193.5Environmental sciencesGE1-350ENEcotoxicology and Environmental Safety, Vol 227, Iss , Pp 112901- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arsenic Brain development Anxiety-like behavior Ten-eleven translocation (TET) activity DNA hydroxymethylation Environmental pollution TD172-193.5 Environmental sciences GE1-350
spellingShingle	Arsenic Brain development Anxiety-like behavior Ten-eleven translocation (TET) activity DNA hydroxymethylation Environmental pollution TD172-193.5 Environmental sciences GE1-350 Jin-Wei Lv Ya-Ping Song Zhi-Cheng Zhang Yi-Jun Fan Fei-Xiang Xu Lan Gao Xiao-Yi Zhang Cheng Zhang Hua Wang De-Xiang Xu Gestational arsenic exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain
description	Several studies found that reduction of 5-hydroxymethylcytosine (5hmC), a marker of DNA hydroxymethylation highly enriched in developing brain, is associated with anxiety-like behaviors. This study aimed to investigate whether gestational arsenic (As) exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain. The dams drank ultrapure water containing NaAsO2 (15 mg/L) throughout pregnancy. Anxiety-like behaviors were evaluated and developing brain 5hmC was detected. Results showed that anxiety-like behaviors were observed in As-exposed adult offspring. In addition, 5hmC content was reduced in As-exposed fetal brain. Despite no difference on Tet1, Tet2 and Tet3 expression, TET activity was suppressed in As-exposed fetal brain. Mechanistically, alpha-ketoglutarate (α-KG), a cofactor for TET dioxygenases, was reduced and Idh2, a key enzymatic gene for mitochondrial α-KG synthesis, was downregulated in As-exposed fetal brain. Of interest, ascorbic acid, a cofactor for TET dioxygenases, reversed As-induced suppression of TET activity. Moreover, ascorbic acid attenuated As-induced reduction of 5hmC in fetal brain. In addition, ascorbic acid alleviated As-induced anxiety-like behaviors in adult offspring. Taken together, these results suggest that gestational As exposure induces anxiety-like behaviors in adult offspring, possibly at part, by inhibiting DNA hydroxymethylation in developing brain.
format	article
author	Jin-Wei Lv Ya-Ping Song Zhi-Cheng Zhang Yi-Jun Fan Fei-Xiang Xu Lan Gao Xiao-Yi Zhang Cheng Zhang Hua Wang De-Xiang Xu
author_facet	Jin-Wei Lv Ya-Ping Song Zhi-Cheng Zhang Yi-Jun Fan Fei-Xiang Xu Lan Gao Xiao-Yi Zhang Cheng Zhang Hua Wang De-Xiang Xu
author_sort	Jin-Wei Lv
title	Gestational arsenic exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain
title_short	Gestational arsenic exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain
title_full	Gestational arsenic exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain
title_fullStr	Gestational arsenic exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain
title_full_unstemmed	Gestational arsenic exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain
title_sort	gestational arsenic exposure induces anxiety-like behaviors in adult offspring by reducing dna hydroxymethylation in the developing brain
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/bcebdf6089234a74b6b8a37f26104355
work_keys_str_mv	AT jinweilv gestationalarsenicexposureinducesanxietylikebehaviorsinadultoffspringbyreducingdnahydroxymethylationinthedevelopingbrain AT yapingsong gestationalarsenicexposureinducesanxietylikebehaviorsinadultoffspringbyreducingdnahydroxymethylationinthedevelopingbrain AT zhichengzhang gestationalarsenicexposureinducesanxietylikebehaviorsinadultoffspringbyreducingdnahydroxymethylationinthedevelopingbrain AT yijunfan gestationalarsenicexposureinducesanxietylikebehaviorsinadultoffspringbyreducingdnahydroxymethylationinthedevelopingbrain AT feixiangxu gestationalarsenicexposureinducesanxietylikebehaviorsinadultoffspringbyreducingdnahydroxymethylationinthedevelopingbrain AT langao gestationalarsenicexposureinducesanxietylikebehaviorsinadultoffspringbyreducingdnahydroxymethylationinthedevelopingbrain AT xiaoyizhang gestationalarsenicexposureinducesanxietylikebehaviorsinadultoffspringbyreducingdnahydroxymethylationinthedevelopingbrain AT chengzhang gestationalarsenicexposureinducesanxietylikebehaviorsinadultoffspringbyreducingdnahydroxymethylationinthedevelopingbrain AT huawang gestationalarsenicexposureinducesanxietylikebehaviorsinadultoffspringbyreducingdnahydroxymethylationinthedevelopingbrain AT dexiangxu gestationalarsenicexposureinducesanxietylikebehaviorsinadultoffspringbyreducingdnahydroxymethylationinthedevelopingbrain
_version_	1718443940119576576

Gestational arsenic exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain

Ejemplares similares