A proteomic analysis of prenatal transfer of microcystin-LR induced neurotoxicity in rat offspring.

Recent studies showed that microcystins (MCs) can be transferred to offspring from their adults and exert notable neurotoxicity, but the exact mechanism is little known. In order to better understand cellular responses in brain tissues disrupted by prenatal transfer of MCs, this work mainly focuses on brain impairments of rat offspring. Pregnant SD rats were infused exposed to microcystin-LR (MCLR) at 10μg/kg body weight (BW)/day or saline solution from gestational day 8 (GD8) to postnatal day 15 (PD15) of lactation. MCLR accumulation, the levels of malondialdehyde (MDA) and acetylcholine esterase (AChE) activity were detected. The results showed that MCLR enhanced toxin accumulation and MDA, but decreased GSH and the level of AChE activity in the brains of rat offspring. MCLR also caused changes to cerebrum ultrastructure, showing a sparse structure, distention of endoplasmic reticulum and swelling mitochondria. To explore the exact mechanisms, we used a proteomic analysis to identify global brain protein profiles. The proteomic results revealed that MCLR remarkably altered the abundance of 49 proteins that were involved in neurodevelopment, oxidative phosphorylation, cytoskeleton, metabolism, protein folding and degradation. Our results indicated that MCLR exerts neurotoxicity mainly by generating oxidative stress and endoplasmic reticulum stress. BIOLOGICAL SIGNIFICANCE: The integration of proteomics and bioinformatics analyses revealed that perinatal exposure to MCLR can occur from mother to offspring and impair the brain of rat pups. MCLR has negative effects on the development of nervous system mainly by generating oxidative stress and endoplasmic reticulum stress.