The Effects Of Gaseous Formaldehyde Exposure On Endogenous Melatonin Metabolism And Cognitive Abilities Of Bal B/c Mice

Formaldehyde is a familiar and decorating indoor air pollutant, which widely used in lumber processing, tissue preservation and textile dyeing. Individuals working in these industries are usually exposed to occupational formaldehyde. The epidemiological and clinical studies have showed that individuals afflicted with occupational formaldehyde exposure often suffered from abnormal behaviors such as aggression, depression, anxiety, sleep disorders, and in particular, cognitive impairments. Coincidentally, clinical patients with melatonin deficiency also complain of cognitive problems associated with above mental disorders. Whether and how FA affects endogenous MT metabolism and induces cognitive decline need to be elucidated.The study includes three levels:animal, molecular cell and in vivo and vitro biochemical reaction. At animal levels, the mice behavior and hippocampus histological changes were respectively evaluated by Morris water maze and H&E staining. Oxidative stress levels in the brain were determined with oxidative markers (reactive oxygen species, glutathione and malondialdehyde). The effects of formaldehyde on endogenous melatonin metabolism were determined with ELISA assay. The endogenous metabolism of formaldehyde and melatonin was measured with stereotaxic injection in vivo and vitro. At cell levels, the reaction of formaldehyde with melatonin was measured with cell toxicity experiments and biochemical study.The results showed that after Bal b/c mice exposed to 3 mg/m3 formaldehyde, in Morris water maze, learning and memory ability are decreased in Bal b/c mice. H&E histological results indicated that pyramidal cells in CA1 region significantly apoptosis after formaldehyde exposure. The results of oxidative makers showed that brain ROS and MDA contents increased significantly with decrease in GSH and MT levels. Inversely, intraperitoneal injection of MT markedly attenuated FA-induced hippocampal neuronal death, restored brain MT levels, and reversed memory decline. Neither gaseous FA exposure nor stereotaxic injection of liquid FA induced significantly increase of endogenous FA. Brain MT contents significantly decreased after FA exposure and stereotaxic injection of liquid FA. After stereotaxic injection of MT, endogenous MT contents significantly decreased, while brain endogenous FA levels significantly increased. Both endogenous FA and melatonin contents have no significant alteration after mixture of FA and MT injection. Biochemical studies indicated that FA can reacts with MT in physical conditions. The results of cell toxicity experiments revealed that both FA and MT have a dose-effect relationship with cell viability, combined action of FA and MT had no significant effect on cell viability.The study showed that cognitive ability of Bal b/c mice declined after 3 mg/m3 FA exposure. FA exposure disrupted oxidative-reductive balance in brain cells, resulting in oxidative stress, reduction of endogenous MT, apoptosis of hippocampus pyramidal neural cells and cognitive disorder. Application of exogenous MT can reverse mice cognitive decline. The underlying reasons for cognitive disorder and protection may lie on the chemical reaction between FA and MT in physical conditions.