title: Reduction of Endogenous Melatonin Accelerates Cognitive Decline in Mice in a Simulated Occupational Formaldehyde Exposure Environment.
abstract: Individuals afflicted with occupational formaldehyde (FA) exposure often suffer from abnormal behaviors such as aggression, depression, anxiety, sleep disorders, and in particular, cognitive impairments. Coincidentally, clinical patients with melatonin (MT) deficiency also complain of cognitive problems associated with the above mental disorders. Whether and how FA affects endogenous MT metabolism and induces cognitive decline need to be elucidated. To mimic occupational FA exposure environment, 16 healthy adult male mice were exposed to gaseous FA (3 mg/m³) for 7 consecutive days. Results showed that FA exposure impaired spatial memory associated with hippocampal neuronal death. Biochemical analysis revealed that FA exposure elicited an intensive oxidative stress by reducing systemic glutathione levels, in particular, decreasing brain MT concentrations. Inversely, intraperitoneal injection of MT markedly attenuated FA-induced hippocampal neuronal death, restored brain MT levels, and reversed memory decline. At tissue levels, injection of FA into the hippocampus distinctly reduced brain MT concentrations. Furthermore, at cellular and molecular levels, we found that FA directly inactivated MT in vitro and in vivo. These findings suggest that MT supplementation contributes to the rescue of cognitive decline, and may alleviate mental disorders in the occupational FA-exposed human populations.
authors.affiliation: Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University, Wuhan 430079, China. meiyufei1990@foxmail.com.|Alzheimer's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China. meiyufei1990@foxmail.com.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Mei
authors.affiliation: Department of Neuobiology, Capital Medical University, Beijing 100069, China. cldduan@ccmu.edu.cn.
authors.forename: Chunli
authors.initials: C
authors.lastname: Duan
authors.affiliation: Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University, Wuhan 430079, China. lixiaoxiao201409@sina.com.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University, Wuhan 430079, China. 18735501894@163.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University, Wuhan 430079, China. cfh723@163.com.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Cao
authors.affiliation: Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University, Wuhan 430079, China. sddy06wendy@sohu.com.
authors.forename: Shuai
authors.initials: S
authors.lastname: Shang
authors.affiliation: Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University, Wuhan 430079, China. dingsm@mail.ccnu.edu.cn.
authors.forename: Shumao
authors.initials: S
authors.lastname: Ding
authors.affiliation: Alzheimer's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China. xiangpei2015@sina.com.
authors.forename: Xiangpei
authors.initials: X
authors.lastname: Yue
authors.affiliation: Department of Neuobiology, Capital Medical University, Beijing 100069, China. gaog@ccmu.edu.cn.
authors.forename: Ge
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Neuobiology, Capital Medical University, Beijing 100069, China. huiyang@ccmu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Alzheimer's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China. imaginary-diva@163.com.
authors.forename: Luxi
authors.initials: L
authors.lastname: Shen
authors.affiliation: Alzheimer's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China. feng402@139.com.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Feng
authors.affiliation: Alzheimer's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China. jjp@ccmu.edu.cn.
authors.forename: Jianping
authors.initials: J
authors.lastname: Jia
authors.affiliation: Alzheimer's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China. tzqbeida@163.com.
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Tong
authors.affiliation: Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University, Wuhan 430079, China. yangxu@mail.ccnu.edu.cn.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
mesh_terms: D000328:Adult; D000818:Animals; D001921:Brain / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000209:etiology*; D005557:Formaldehyde / Q000009:adverse effects*; D006624:Hippocampus / Q000187:drug effects*; D006801:Humans; D008297:Male; D008550:Melatonin / Q000502:physiology*; D008568:Memory / Q000187:drug effects*; D051379:Mice; D016273:Occupational Exposure; D018384:Oxidative Stress / Q000187:drug effects; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*
chemical_list: D005557:Formaldehyde; D008550:Melatonin
keywords: ">l-glutathione; formaldehyde (FA); melatonin (MT); oxidative stress; reactive oxygen species; spatial memory