Effects of early-life exposure and adulthood re-challenge to paraquat on motor ability of C57BL/6 mice

Background Animals are highly susceptible to environmental neurotoxicants during early life, and tend to sustain life-long injuries. Adulthood exposure to paraquat (PQ), a widely applied herbicide, can cause Parkinson's disease-like impaired motor function symptoms. There are limited studies, however, on the effects of exposure to PQ during early life and re-exposure in adult life on the motor function of the elderly.

Objective This experiment investigates the effects of early-life exposure to PQ on the motor function of male and female C57BL/6 mice, and the effects of adult-life re-challenge to PQ on the motor function of male C57BL/6 mice.

Methods Male and female C57BL/6 mice at 5 days old were divided into two groups of each sex, with 16 male mice in each male group and 8 female mice in each female group. The control groups received normal saline (NS), while the PQ groups received intraperitoneal injection of 0.8 mg·kg^-1 PQ, once a day, for consecutive 15 d. At 8 months old, the male mice treated with NS or PQ in early life were further divided into two groups of each treatment, with 8 mice in each group. The NS+NS group and the PQ+NS group additionally received NS administration, and the NS+PQ group and the PQ+PQ group additionally received 10 intraperitoneal injections of PQ (10mg·kg^-1), once every other day. At 22 months old, a gait analysis system was employed to assess the motor function of the mice.

Results Early-life exposure to PQ decreased the regularity indexmale NS group:(95.12±2.79)%; male PQ group:(85.04±2.33)%, the foot area of right forelimbmale NS group:(0.317±0.004) m²; male PQ group:(0.272±0.010) m², and the stride of right forelimbmale NS group:(6.38±0.11)cm; male PQ group:(5.14±0.33) cm of the male mice at 22 months of age, and also increased the number of steps (male NS group:18.00±1.04; male PQ group:24.38±1.71) and the run duration of right forelimbmale NS group:(0.286±0.001) s; male PQ group: (0.315±0.014) s (P < 0.05). Early-life PQ treatment had no impacts on motor function of female mice (P>0.05). After re-challenge to PQ in adulthood, compared with NS+PQ treatment, PQ+PQ treatment significantly increased the number of steps (NS+PQ group:19.88±0.72; PQ+PQ group:29.00±1.52), decreased the regularity indexNS+PQ group:(94.82±2.85)%; PQ+PQ group:(88.32±2.02)%, increased the run duration of right forelimbNS+PQ group:(0.336±0.010)s; PQ+PQ group:(0.384±0.119)s, decreased the foot area of right forelimbNS+PQ group: (0.307±0.008)m²; PQ+PQ group:(0.260±0.114)m², decreased the swing speed of right forelimbNS+PQ group:(38.61±1.62)cm·s^-1; PQ+PQ group: (26.52±1.38)cm·s^-1, and decreased the stride of right forelimbNS+PQ group:(6.24±0.24)cm; PQ+PQ group:(4.70±0.27)cm (P < 0.05).

Conclusion Early-life exposure to low-dose PQ can cause irreversible motor function impairments, and enhance the vulnerability to subsequent adulthood insults in male mice, but such effects are not observed in female mice, suggesting that male rodent animals are more sensitive to PQ in regard of motor behavior defects.