Wang_2014_Inhal.Toxicol_26_250

Abstract To investigate effects of neurobehavioral disturbances in mice caused by sub-chronic exposure to low-dose volatile organic compounds (VOCs) and the possible mechanism for these effects, 60 male Kunming mice were exposed in 5 similar static chambers, 0 (control) and 4 different doses of VOCs mixture (G1-4) for consecutively 90 d at 2 h/d. The concentrations of VOCs mixture were as follows: formaldehyde, benzene, toluene, and xylene 0.05 + 0.05 + 0.10 + 0.10 mg/m(3), 0.10 + 0.11 + 0.20 + 0.20 mg/m(3), 0.50 + 0.55 + 1.00 + 1.00 mg/m(3), 1.00 +1.10 + 2.00 + 2.00 mg/m(3), respectively, which corresponded to 1/2, 1, 5, and 10 times of indoor air quality standard in China. Morris water maze (MWM) and Grip strength (GS) test were performed in the last 7 weeks. One day following VOCs exposure, oxidative stress markers, neurotransmitters, and cholinergic system enzymes in brain were examined. In addition, the expressions of N-methyl-d-aspartate (NMDA) receptor in hippocampus were determined. VOCs exposure induced behavioral impairment of mice in MWM and GS test. The levels of reactive oxygen species (ROS), malondialdehyde (MDA) and glutamic acid (Glu) were significantly increased, while the acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and acetylcholine (ACh) levels, and the expression of NMDA receptor were significantly decreased in VOCs exposed groups. Results showed that sub-chronic exposure to low-dose VOCs induced damage on physique and motor function, as well as impairment on learning and memory capacity of mice. Oxidative damage, abnormal metabolism of neurotransmitters and cholinergic system enzymes, and the alternation of NMDA receptor expression may be the possible mechanism for VOCs-induced neurotoxicity.