title: Subchronic Exposure to Arsenic Represses the TH/TRβ1-CaMK IV Signaling Pathway in Mouse Cerebellum.
abstract: We previously reported that arsenic (As) impaired learning and memory by down-regulating calmodulin-dependent protein kinase IV (CaMK IV) in mouse cerebellum. It has been documented that the thyroid hormone receptor (TR)/retinoid X receptor (RXR) heterodimer and thyroid hormone (TH) may be involved in the regulation of CaMK IV. To investigate whether As affects the TR/RXR heterodimer and TH, we determined As concentration in serum and cerebellum, 3,5,3'-triiodothyronine (T3) and thyroxin (T4) levels in serum, and expression of CaMK IV, TR and RXR in cerebellum of mice exposed to As. Cognition function was examined by the step-down passive avoidance task and Morris water maze (MWM) tests. Morphology of the cerebellum was observed by Hematoxylin-Eosin staining under light microscope. Our results showed that the concentrations of As in the serum and cerebellum of mice both increased with increasing As-exposure level. A significant positive correlation was found between the two processes. Adeficit in learning and memory was found in the exposed mice. Abnormal morphologic changes of Purkinje cells were observed in cerebellum of the exposed mice. Moreover, the cerebellar expressions of CaMK IV protein and the TRβ gene, and TRβ1 protein were significantly lower in As-exposed mice than those in controls. Subchronic exposure to As appears to increase its level in serum and cerebella of mice, impairing learning and memory and down-regulating expression of TRβ1 as well as down-stream CaMK IV. It is also suggested that the increased As may be responsible for down-regulation of TRβ1 and CaMK IV in cerebellum and that the down-regulated TRβ1 may be involved in As-induced impairment of learning and memory via inhibiting CaMK IV and its down-stream pathway.
authors.affiliation: Department of Obstetrics and Gynecology, General Hospital of Beijing Military Command, Beijing 100700, China. greeneve@163.com.|Department of Obstetrics and Gynecology, No. 210 Hospital of PLA, Dalian 116021, China. greeneve@163.com.
authors.forename: Huai
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, Dalian 116044, China. lsy236@163.com.
authors.forename: Shuangyue
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Microecology, Dalian Medical University, Dalian 116044, China. guoyanjie829@163.com.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Obstetrics and Gynecology, No. 210 Hospital of PLA, Dalian 116021, China. liuxiaofengdl210@163.com.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Bayi Brain Diseases Hospital Affiliated to General Hospital of Beijing Military Command, Beijing 100700, China. yyeditor@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Editorial Department, Journal of Dalian Medical University, Dalian 116044, China. green15015@163.com.
authors.forename: Jinqiu
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044, China. lisheng_1996@163.com.
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Public Health, Dalian Medical University, Dalian 116044, China. Congzhang1203@hotmail.com.
authors.forename: Cong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, General Hospital of Beijing Military Command, Beijing 100700, China. guanhuai_submit@163.com.
authors.forename: Lixin
authors.initials: L
authors.lastname: Shang
authors.affiliation: Department of Occupational and Environmental Health, Dalian Medical University, Dalian 116044, China. piaofengyuan353@163.com.
authors.forename: Fengyuan
authors.initials: F
authors.lastname: Piao
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007859:Learning Disabilities / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D047488:Retinoid X Receptors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism; D059550:Toxicity Tests, Subchronic
chemical_list: D047488:Retinoid X Receptors; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D001151:Arsenic
keywords: CaMK IV; arsenic; cerebellum; retinoid X receptor; thyroid hormone receptor
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