Attention deficit hyperactivity disorder-like behavior induced by hypoxia in mice and its synaptic damage mechanism
Journal Title: Journal of Air Force Medical University - Year 2023, Vol 44, Issue 3
Abstract
Objective To explore the attention deficit hyperactivity disorder ( ADHD)-like behavior induced by hypoxia in mice and its synaptic damage mechanism. Methods The 3-week-old C57BL / 6 male mice were randomly divided into control group and hypoxia group, with 15 mice in each group. The hypoxia group was placed in the high altitude simulation cabin at a simulated 6 000 m altitude for 14 d of hypoxia exposure. The open field test, Y maze test and elevated plus maze test were used to observe the behavior of mice. The ultrastructure of synapses in prefrontal cortex and striatum was observed by transmission electron microscopy. The detection kits were used to detect the contents of hydrogen peroxide, reactive oxygen species ( ROS ), malondialdehyde ( MDA ) and reduced glutathione ( GSH) in prefrontal cortex and striatum, as well as the activities of glutathione peroxidase ( GSH-PX) and total superoxide dismutase ( T-SOD). The expression levels of brain-derived neurotrophic factor ( BDNF) and glial cell line-derived neurotrophic factor ( GDNF) in prefrontal cortex and striatum were detected by real-time quantitative PCR and Western blotting. Results Compared with the control group, the total movement distance and movement speed of mice in hypoxia group increased in the open field test (P < 0. 01), and the quiescent time decreased (P < 0. 01). The autonomous alternation rate decreased in the Y maze test (P < 0. 05). In the elevated plus maze test, there was no significant change in the entering times and exploration time of open arm (P > 0. 05), but the freezing time decreased ( P < 0. 05). The synapses in prefrontal cortex and striatum were slightly swollen, blurred and stained shallowly. In prefrontal cortex and striatum, the contents of hydrogen peroxide, ROS and MDA increased (P < 0. 05), and the protein and mRNA expressions of BDNF and GDNF decreased (P < 0. 01). In prefrontal cortex, the GSH content decreased significantly (P < 0. 01) and the activities of GSH-PX and T-SOD decreased (P < 0. 05). The activity of T-SOD in striatum also decreased (P < 0. 05). Conclusion Hypoxia exposure can lead to ADHD-like behavior and synaptic structure damage in mice, which is related to redox imbalances and decreased expression of neurotrophic factors in prefrontal cortex and striatum.
Authors and Affiliations
ZHAO Ziyu, LIU Qiling, YAO Jinyu, DONG Xiaoru, DONG Qian, WANG Tao, ZHOU Yang, CAO Zipeng
Keywords
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