The role of DAAO in arsenic exposure induced learning and memory impairment in offspring mice
10.3760/cma.j.cn231583-20231009-00079
- VernacularTitle:DAAO在砷暴露致仔鼠学习记忆损害中的作用
- Author:
Xiaoxia JIN
1
;
Jiaqi SUN
;
Huan WANG
;
Yan WANG
Author Information
1. 沈阳医学院公共卫生学院职业卫生与职业医学教研室，沈阳 110034
- Keywords:
Arsenic poisoning;
D-serine;
D-amino acid oxidase;
N-methyl-D-aspartate receptor
- From:
Chinese Journal of Endemiology
2024;43(6):440-445
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of D-amino acid oxidase (DAAO) in arsenic exposure induced learning memory impairment in offspring mice.Methods:Eighteen Kunming pregnant mice were randomly divided into a non-treatment group (distilled water, n = 6) and an arsenic exposed group [60 mg/L sodium arsenite (NaAsO 2) in drinking water, n = 12] by randomized numerical table method. From the first day of pregnancy until weaning, the mother mice were exposed to arsenic. After weaning, the offspring mice were exposed to arsenic through free drinking water until the end of the experiment. Six weeks after birth, the offspring mice of the arsenic exposed group were divided into a NaAsO 2 group and a NaAsO 2 + DAAO inhibitor 6-chlorobenzo [d] isoxazol-3-ol (CBIO) group according to the group of mother mice. The offspring mice of non-treatment group as the control group. The offspring mice of the control group and NaAsO 2 group were given intraperitoneal injection of 0.5% sodium carboxymethylcellulose, while the NaAsO 2 + CBIO group was given intraperitoneal injection of 60 mg/kg CBIO for two consecutive weeks. At the end of the intervention, the spatial learning and memory abilities of the offspring mice were measured using a Y-maze experiment. After cardiac perfusion, brain tissue was taken from the offspring mice and the hippocampus was isolated. Hematoxylin-eosin (HE) staining was used to observe the morphology of the hippocampal neurons in the offspring mice. D-serine content was determined by ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-MS/MS). The mRNA levels of synaptophysin (SYP), synaptosomal-associated protein 25 (SNAP25), postsynaptic density 95 (PSD95), DAAO, and N-methyl-D-aspartate receptor (NMDAR) subunits NR1, NR2A, NR2B were measured by real-time fluorescence quantitative PCR. Results:There was a statistically significant difference in the offspring mice alternating response rate of the Y-maze experiment among the control, NaAsO 2, and NaAsO 2 + CBIO groups [ (58.06 ± 3.78) %, (48.61 ± 5.75)%, (56.25 ± 6.76)%, F = 4.87, P = 0.023], and the NaAsO 2 group was significantly lower than the control and NaAsO 2 + CBIO groups ( P < 0.05). The HE staining results showed that the control group had a higher number of neuronal cells in the CA1 and CA3 regions of the hippocampal tissue, and they were in good condition. The number of neuronal cells in the NaAsO 2 group decreased, with irregular morphology and unclear cell contours. The NaAsO 2 + CBIO group had a higher number of neuronal cells, improved cell morphology and contour, and reduced tissue damage. There were statistically significant differences in D-serine content and mRNA levels of SYP, SNAP25, PSD95, DAAO, NR1, NR2A, and NR2B in the hippocampus of the offspring mice from the control, NaAsO 2, and NaAsO 2 + CBIO groups ( F = 5.41, 4.41, 10.16, 7.60, 6.98, 5.63, 6.53, 4.33, P = 0.017, 0.031, 0.002, 0.005, 0.007, 0.015, 0.009, 0.033). Among them, the D-serine content and mRNA levels of SYP, SNAP25, PSD95, NR1, and NR2B in the hippocampus of the NaAsO 2 group were significantly lower than those in the control group and NaAsO 2 + CBIO group, the mRNA level of NR2A was significantly lower than that in the control group, and the mRNA level of DAAO was significantly higher than that in the control and NaAsO 2 + CBIO groups ( P < 0.05). Conclusions:Arsenic exposure can induce the learning and memory impairment in offspring mice, reduce D-serine content in the hippocampus, as well as the transcription level of NMDAR subunits and synapse-associated proteins, up-regulate the transcription levels of DAAO; and inhibit DAAO, leading to increased D-serine content, the transcription levels of NMDAR subunits and synapse-associated proteins, improving arsenic exposure induced learning and memory impairment in the offspring mice.
