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Int. J. Environ. Res. Public Health 2016, 13(3), 258; doi:10.3390/ijerph13030258

Reduction of Endogenous Melatonin Accelerates Cognitive Decline in Mice in a Simulated Occupational Formaldehyde Exposure Environment

1
Section of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal University, Wuhan 430079, China
2
Alzheimer’s Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China
3
Department of Neuobiology, Capital Medical University, Beijing 100069, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Paul B. Tchounwou
Received: 25 November 2015 / Revised: 20 January 2016 / Accepted: 27 January 2016 / Published: 29 February 2016
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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. View Full-Text
Keywords: formaldehyde (FA); melatonin (MT); oxidative stress; spatial memory; reactive oxygen species; l-glutathione formaldehyde (FA); melatonin (MT); oxidative stress; spatial memory; reactive oxygen species; l-glutathione
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Mei, Y.; Duan, C.; Li, X.; Zhao, Y.; Cao, F.; Shang, S.; Ding, S.; Yue, X.; Gao, G.; Yang, H.; Shen, L.; Feng, X.; Jia, J.; Tong, Z.; Yang, X. Reduction of Endogenous Melatonin Accelerates Cognitive Decline in Mice in a Simulated Occupational Formaldehyde Exposure Environment. Int. J. Environ. Res. Public Health 2016, 13, 258.

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