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1. Introduction
Although formaldehyde (FA) is generally considered an environmental pollutant [1] and neurotoxic substance [2], it is an indispensable raw material for hospital preservation, industrial activities, and agriculture disinfectant [3]. Hence, a large number of workers are exposed to FA [4]. Epidemiological studies have shown that work-related exposure to FA results in headaches, anxiety, fatigue, sleep disorders, and in particular, cognitive disorders [5,6]. Accordingly, the results of animal experiments reveal that gaseous FA exposure induces abnormal behaviors, such as: aggression, depression, a decline in locomotor activity, and spatial memory deficits [7,8,9]. Surprisingly, studies have indicated that healthy rats that have been exposed to abnormally high concentrations of gaseous FA have normal levels of FA in the brain [10,11,12]. Therefore, which endogenous factor is the molecular target of FA remains largely unknown.
Endogenous melatonin (MT), N-acetyl-5-methoxytryptamine, is a hormone present in mammalian brains, including humans [13,14,15], which is involved in the entrainment (synchronization) of circadian rhythms of various physiological functions including sleep patterning, blood pressure regulation, moodiness [16,17], and memory [18]. As well as occupational FA-exposed workers, those with mental abnormalities, clinical patients with mild cognitive impairments, and Alzheimer’s disease (AD), also exhibit abnormal behaviors such as aggression or depression, anxiety, insomnia, and cognitive decline [19,20,21]. Notably, a marked elevation in FA levels [22,23] associated with a reduction in MT is observed in the serum and postmortem cerebrospinal fluid of patients suffering from AD [24,25,26]. Previous studies suggest that application of MT can reverse cognitive decline in FA-exposed animal models [27,28], and mental illness in human [29,30,31]. These data strongly suggest that endogenous MT deficiency is a possible reason for occupational FA exposure-related cognitive impairments and mental disorders.
In the present study, we found that under a simulated occupational FA exposure environment, mice exposed to FA displayed spatial memory decline associated with MT reduction in the brains. Furthermore, both in vitro and in vivo experimental results indicated that FA can directly inactivate MT. Therefore, supplementation of MT (a powerful brain antioxidant), can reduce the effects of FA-induced brain oxidative stress, and possibly reverse cognitive impairments. Finally, possible roles of deficiencies in brain derived MT in mental disorders are also discussed.
2. Methods
2.1. Animals
All specified pathogen-free adult male Bal b/c mice (6 weeks old,...