DNA methylation changes in the hippocampus of learning and memory disorder offspring rats of lead exposure during pregnant and lactation period.

BACKGROUND: Pregnant female rats exposed to lead may give birth to offspring with learning and memory disorders. Many studies have shown that there are many mechanisms that cause learning and memory impairment. Epigenetic mechanisms may play an important function in the learning and memory impairment. METHODS: We examined DNA methylation changes in the hippocampus of rats with learning and memory disorder that were the offsprings of rats exposed to lead during pregnant and lactation period. The Morris Water Maze was applied as a learning and memory test, and a Roche NimbleGen's rat DNA methylation 385K Promoter Plus CpG Island Array was used for array hybridization. RESULTS: The results of the integrated navigation and spacial exploration test showed that until 21 days after birth and the lactation period, the learning and memory abilities of offsprings with lead exposure during pregnant and lactation period were significantly lower than those of the control group. The hippocampus DNA methylation levels of the three types of promoters increased compared with those of the control group. According to the Gene Ontology (GO) terms, metal ion transport, cell connections, the lamellar body, the axon bulge, and methylation of various metal transporters were found to be significantly enriched. Pathway analysis showed that the hedgehog signaling pathway, neuroactive receptor-ligand interaction with the ligase pathway, and interaction between cytokines had high methylation. CONCLUSIONS: DNA methylation of the whole genome in the hippocampus of the rats with learning and memory impairment induced by perinatal lead contact showed a lot of changes compared with that in the group of control.

[Suppression subtractive hybridization for the identification of differentially expressed genes in the hippocampus of the offsprings of lead exposed female rats].

OBJECTIVE: To screen and identify differentially expressed genes in the hippocampus of the offsprings of lead exposed female rats in order to provide a theoretical basis for identifying learning and memory deficits related genes. METHODS: RNA was extracted from the hippocampus of young rats with learning and memory deficits due to maternal lead exposure. Suppression subtractive hybridization was used to identify the differentially expressed genes in the hippocampus. RESULTS: An effective subtracted library was constructed which consisted of approximately 200 clones. Sequencing for the library identified 93 clones harboring insertion fragments which included 43 different genes and 4 unknown genes. These genes might be related to learning and memory deficits due to maternal lead exposure. CONCLUSIONS: The up-regulated genes in the hippocampus of young rats from pregnant rats under lead exposure include some housekeeping genes and some proteins involved in cellular protein folding, signal transduction, stress response and DNA methylation. These proteins might be directly related to a significant reduction in learning and memory abilities in the young rats.