The Change of DNA Methyltransferase in Mice with Spatial Learning and Memory Impairment Induced by Benzoapyrene

Objectives To investigate the change of DNA methyltransferase (DNMT) mRNA levels and their kinase activities in ICR mice with learning and memory impairment induced by benzoapyrene(BaP).

Methods Forty-eight adult male ICR mice were categorized randomly into 4 groups based on body weight, one solvent control group and three BaP-treated groups at the dosage of 0.5 mg/kg (low-dose), 2 mg/kg (mid-dose) and 10 mg/kg (high-dose). BaP-treated mice were intra-peritoneally injected with BaP once every two days for 30 times of administration. At the end of 30^th administration, Morris water maze test was used to determine the spatial learning and memory ability of mice. The change of DNMT1, DNMT3a and DNMT3b mRNA levels were detected by using a real-time fluorescence quantitative-polymerase chain reaction (qPCR), and the DNMT1, DNMT3a and DNMT3b kinase activity were determined by using an enzyme linked immunosorbent assay (ELISA) at the end of 10^th, 20^th and 30^th administration.

Results Morris water maze test showed an increase of average escape latency time with the dose of BaP injected in mice, the escape latency time was significantly longer in the high-dose group than that in the solvent control group (P < 0.05). The frequency of crossing platform and the swimming distance in the target quadrant were gradually decreased with the dose of BaPs, which were both significantly increased in the high-dose group as compared to the solvent control group (P < 0.05). Compared with the solvent control group, DNMT1, DNMT3a and DNMT3b mRNA levels and their kinase activities were significantly increased in cerebral cortex in BaP-treated groups (P < 0.05), and were significantly dependent on the duration and the dose of BaP administration (P < 0.05).

Conclusions BaP administration could result in the increase of DNMT1, DNMT3a and DNMT3b mRNA levels and their kinase activities in cerebral cortex in mice, which might be the potential critical mechanism of learning and memory deficits induced by BaP.