title: A proteomic analysis of prenatal transfer of microcystin-LR induced neurotoxicity in rat offspring.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, Chinese Academy of Sciences, Donghu South Road 7, Wuhan 430072, China; School of Public Health, Anhui Medical University, Hefei 230032, China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: ligy2001@163.com.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Li
authors.affiliation: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, Chinese Academy of Sciences, Donghu South Road 7, Wuhan 430072, China. Electronic address: chenjun@ihb.ac.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008387:Marine Toxins; D052998:Microcystins / Q000633:toxicity*; D020258:Neurotoxicity Syndromes / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008387:Marine Toxins; D052998:Microcystins; C057862:cyanoginosin LR; D005978:Glutathione
keywords: Generation transfer; MCLR; Neurotoxicity; Offspring; Proteomics