Maternal stress during pregnancy leads to ADHD like behavior in offspring mice and its mechanism / 中华行为医学与脑科学杂志

ABSTRACT

Objective:To investigate the attention deficit/hyperactivity disorder(ADHD) like behavior of offspring mice induced by stress during pregnancy and its mechanism.Methods:Chronic unpredictable stress was applied to ICR pregnant mice in different gestational periods. The offspring mice were randomly selected and the behavior changes of each group were observed in open field experiment (CG control group; SG1 cums stress stimulation from 8 to 14 days of gestation; SG2 cums stress stimulation from 15 days of gestation to childbirth). The plasma concentrations of GABA, its metabolic enzymes and dopamine were detected by ELISA.Results:The results of open field experiment showed that the total distance, the time of stay in central area, the speed in central area, and the speed in surrounding area in SG1 group, SG2 group and CG group were statistically significant ( F=8.30, 5.01, 8.05, 7.15, all P<0.05). The total distances of SG1 group and SG2 group were significantly longer than that of CG group ((5 221.07±469.95)mm, (4 825.63±545.49)mm, (3 781.17±111.34)mm, both P<0.05).The times of stay in central area of SG1 and SG2 groups were shorter than that in CG group ((5.95±3.32)s, (8.59±3.42)s, (11.10±3.61)s, all P<0.05). The speeds in central area of SG1 and SG2 groups were faster than that of CG group ((30.93±5.79)mm/s, (32.48±9.06)mm/s, (20.57±5.07)mm/s, all P<0.05).The speed in surrounding area in SG1 group was faster than that in CG group ((16.91±1.64)mm/s), (12.42±3.77)mm/s, P<0.05). ELISA results showed that there were significant differences in mice plasma GABA, GAD65, GAD67 and DA among CG group, SG1 group and SG2 group ( F=16.52, 6.42, 11.04, 7.26, all P<0.05).The plasma concentrations of GABA in SG1 group and SG2 group were lower than that in CG group ((3.70±0.80)μmol/L, (4.40±0.80)μmol/L, (6.06±1.01)μmol/L, all P<0.05).The plasma concentrations of GAD65 ((5.36±0.75)μg/L, (6.99±1.01)μg/L, P<0.05)and GAD67((10.52±1.09)μg/L, (9.84±1.35)μg/L, (12.83±1.67)μg/L, P<0.05)in SG1 group were lower than those in CG group. The plasma DA concentration in SG1 group ((82.81±8.59)ng/L) was higher than that in CG group ((69.43±9.42)ng/L, P<0.05) and SG2 group ((66.36±10.77)ng/L, P<0.05). Conclusion:Prenatal stress can induce ADHD-like behavioural phenotypes in offspring mice, which may be related to the influence of plasma GABA metabolism and DA concentration.