Study On Effects And Mechanisms Of VOCs Induced Dysfunction On Learning And Memory Capacity Of Mice

Volatile Organic Compounds (Volatile Organic Compounds, VOCs) are one of the most common indoor air pollutants. Formaldehyde, benzene, toluene and xylene are typical indoor volatile organic compounds. VOCs can induce toxic effects including the effects of airway inflammation, reproductive toxicity, immunotoxicity, genotoxicity, neurotoxicity, and many other aspects. Because neurobehavioral toxicology is one of the most common and sensitive effects that VOCs will induce, so the present study was designed to explore the effects and mechanisms of VOCs induced dysfunction on learning and memory capacity. We used gas mixed exposure model, in which VOCs were chose as the test substance, Kunming male mice were used as the experimental animal. We evaluated the effects that VOCs will induce on learning and memory capacity and grip strength. We also analyzed oxidative damage, levels of neurotransmitter and neurotrophin in brain, expression of N-methyl-D-aspartate (NMDA) receptor subunits NR1, NR2A and NR2B in hippocampus.The present study indicated that VOCs induced dysfunction on learning and memory capacity, which were demonstrated by the longer time needed to find the escape latency in the hidden platform acquisition test and the shorter swimming time spent in the target quadrant during the spatial probe test. In acute exposure experiment, mice in the control spent (45.8±2.8) s in the target quadrant during the probe test. It is significant longer than group2(36.7±1.7) s、group3(27.1±1.1) s and group4(25.9±2.8) s, in which VOCs levels were respectively corresponded to30、50、100times of Indoor Air Quality Standard. There were also significant decreases on grip strength in both VOCs subchronic and VOCs, bacteria, particular matters acute exposure experiments.Neurobehavioral changes were also accompanied by the abnormal expression of biochemical indicators. There were significant increase of ROS and MDA, decrease of GSH level in brain. The content of glutathione (Glu) increased, while the content of acetylcholine (Ach), activity of Tcetylcholinesterase (TChE) and acetylcholine transferase (ChAT) decreased as compared to the control group. Meanwhile, the level of brain-derived neurotrophic factor (BDNF), glial cell-derived trophic factor (GDNF) and nerve growth factor (NGF) in mice brain showed decreasing trends when exposed to VOCs, bacteria and particulate matter. There were overall descenting trends in the expression of NR1, NR2A and NR2B subunits in hippocampus, although with slightly increased trends initially and there were significant decreases in higher VOCs level groups. The results of hippocampus morphology showed that the total number of granule cells and pyramidal neurons in higher level groups were reduced as compared to the control, meanwhile karyopycnosis and karyolysis were also observed.The present study indicated that VOCs can induce dysfunction on learning and memory capacity, the possible mechanism might be speculated as the excessive reactive free radicals (ROS) and peroxidation products (MDA) which generated by oxidative damage can destroy nerve cell membranes, resulting in abnormal release of neurotransmitter Ach and Glu; Meanwhile, the production and transportation of BDNF, NGF and GDNF were blocked after exposed to VOCs. As a result, the activity of ChAT, TChE and other enzymes activity were inhibited; the expression and release of Ach were also decreased. Therefore, the neural excitatory or inhibitory toxicity induced by oxidative damage, the generation and transportation of neurotrophin were blocked can both cause abnormal expression of neurotransmitter, which induced excessive excitatory or inhibitory toxicity of amino acid receptor including NMDA receptor, caused dysfunction on learning and memory capacity eventually.