Impairment of learning and memory of mice offspring at puberty, young adulthood, and adulthood by low-dose Cd exposure during pregnancy and lactation via GABA_AR α5 and δ subunits

摘要

Cadmium (Cd) is a pervasive carcinogen and environmental endocrine disruptor. We studied the changes in learning and memory of offspring mice, whose mothers were exposed to 10 mg Cd/L via the drinking water during pregnancy and lactation period, as well as the changes of testosterone and estrogen levels, serum Cd levels, the histopathological changes and the changes in the mRNA and protein levels of different subunits of gamma-aminobutyric acid receptor subtype A subunits (GABAARs) in the hippocampus at the prepuberty, puberty, young adult, and adult stages.At birth, Cd had no obvious effect on mice offspring as statistically accessed based on their body weight, body length, and tail length (all p > 0.05). After grouped, the serum Cd levels increased in the three exposed groups more than in the normal control group at stages (all p < 0.05). Only serum estradiol of female offspring at age 7 weeks was significantly decreased compared with other groups (all p < 0.05). Histopathological results showed that the arrangement of the cells in hippocampal CA1 area of mice offspring was significantly sparse in the exposed groups compared with the control group.At 5 and 7 weeks, two Cd-exposed groups showed prolonged escape latency and exploring time for the platform compared with the normal group in the Morris water maze (all p < 0.05). Only increased protein expression of GABA(A)R alpha 5 was found in the Cd group at these two ages. At age 12 weeks, similar impaired learning and memory of female mice, and decreased protein expression of GABA(A)R was found in Cd-exposed groups.Collectively, low-dose Cd had no effect on the growth of mice offspring but affected their learning and memory, especially female offspring, at puberty, young adulthood, and adulthood through changed structure in the hippocampal CAl area and protein expression of GABA(A)R5 and GABA(A)RS.