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Comparison Impairments of Spatial Cognition and Hippocampal Synaptic Plasticity Between Prenatal and Postnatal Melamine Exposure in Male Adult Rats

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Abstract

Our previous investigation showed that melamine in offspring hippocampus appeared to not be the critical factor for cognitive defects. The present study was to investigate whether the cognitive impairments induced by prenatal and postnatal melamine exposure and persisted into adulthood, and to evaluate the differences of the exposures in affecting hippocampus-depended cognition and synaptic plasticity. Wistar rats were exposed to melamine through the whole gestational period or from postnatal day (PD) 21 to PD41, and then tested on PD90. The experiments of water maze and hippocampal synaptic plasticity in vivo were performed to assess the effects on spatial cognition and synaptic impairments. The results indicated that cognitive defects were induced by exposures to either prenatal or postnatal melamine, whereas there was a more serious damage in prenatal. Histological evidence further showed that there were the detrimental effects of both prenatal and postnatal effects. Paired-pulse facilitation ratio and post-tetanic potentiation were severely impacted in prenatal-exposed rats but not postnatal-exposed ones. Both exposures to prenatal and postnatal melamine impaired long-term potentiation, while there was severe damage to prenatal animals. These data suggest that the detrimental effects of prenatal and postnatal melamine on cognition and hippocampal synaptic plasticity could persist into adulthood, and the impairment of prenatal exposure was to some extent more severe. Hence, prenatal and postnatal exposures to melamine may have different effects on hippocampus-dependent learning and memory, which would most likely result from differentially adversely properties on the hippocampal CA1 synaptic function.

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References

  • Aisa B, Tordera R, Lasheras B, Del Rio J, Ramirez MJ (2007) Cognitive impairment associated to HPA axis hyperactivity after maternal separation in rats. Psychoneuroendocrinology 32:256–266

    Article  PubMed  CAS  Google Scholar 

  • An L, Zhang T (2013) Spatial cognition and sexually dimorphic synaptic plasticity balance impairment in rats with chronic prenatal ethanol exposure. Behav Brain Res 256:564–574

    Article  PubMed  CAS  Google Scholar 

  • An L, Zhang T (2014a) Prenatal melamine exposure induces impairments of spatial cognition and hippocampal synaptic plasticity in male adolescent rats. Reprod Toxicol 49:78–85

    Article  PubMed  CAS  Google Scholar 

  • An L, Zhang T (2014b) Vitamins C and E reverse melamine-induced deficits in spatial cognition and hippocampal synaptic plasticity in rats. Neurotoxicology 44:132–139

    Article  PubMed  CAS  Google Scholar 

  • An L, Zhang T (2015) Prenatal ethanol exposure impairs spatial cognition and synaptic plasticity in female rats. Alcohol 49:581–588

    Article  PubMed  CAS  Google Scholar 

  • An L, Li Z, Yang Z, Zhang T (2011) Cognitive deficits induced by melamine in rats. Toxicol Lett 206:276–280

    Article  PubMed  CAS  Google Scholar 

  • An L, Li Z, Yang Z, Zhang T (2012a) Melamine induced cognitive impairment associated with oxidative damage in rat’s hippocampus. Pharmacol Biochem Behav 102:196–202

    Article  PubMed  CAS  Google Scholar 

  • An L, Liu S, Yang Z, Zhang T (2012b) Cognitive impairment in rats induced by nano-CuO and its possible mechanisms. Toxicol Lett 213:220–227

    Article  PubMed  CAS  Google Scholar 

  • An L, Yang Z, Zhang T (2013a) Imbalanced synaptic plasticity induced spatial cognition impairment in male offspring rats treated with chronic prenatal ethanol exposure. Alcohol Clin Exp Res 37:763–770

    Article  PubMed  CAS  Google Scholar 

  • An L, Yang Z, Zhang T (2013b) Melamine induced spatial cognitive deficits associated with impairments of hippocampal long-term depression and cholinergic system in Wistar rats. Neurobiol Learn Mem 100:18–24

    Article  PubMed  CAS  Google Scholar 

  • An L, Fu J, Zhang T (2015) Reversible effects of vitamins C and E combination on cognitive deficits and oxidative stress in the hippocampus of melamine-exposed rats. Pharmacol Biochem Behav 132:152–159

    Article  PubMed  CAS  Google Scholar 

  • Bailey SA, Zidell RH, Perry RW (2004) Relationships between organ weight and body/brain weight in the rat: what is the best analytical endpoint? Toxicol Pathol 32:448–466

    Article  PubMed  Google Scholar 

  • Baynes RE, Smith G, Mason SE, Barrett E, Barlow BM, Riviere JE (2008) Pharmacokinetics of melamine in pigs following intravenous administration. Food Chem Toxicol 46:1196–1200

    Article  PubMed  CAS  Google Scholar 

  • Blokland A, Geraerts E, Been M (2004) A detailed analysis of rats’ spatial memory in a probe trial of a Morris task. Behav Brain Res 154:71–75

    Article  PubMed  Google Scholar 

  • Bondy SC, Campbell A (2005) Developmental neurotoxicology. J Neurosci Res 81:605–612

    Article  PubMed  CAS  Google Scholar 

  • Chen JS (2009) A worldwide food safety concern in 2008–melamine-contaminated infant formula in China caused urinary tract stone in 290,000 children in China. Chin Med J (Engl) 122:243–244

    Article  Google Scholar 

  • Chu CY, Chu KO, Ho CS, Kwok SS, Chan HM, Fung KP, Wang CC (2013) Melamine in prenatal and postnatal organs in rats. Reprod Toxicol 35:40–47

    Article  PubMed  CAS  Google Scholar 

  • Chung MK, Kim CY, Kim JC (2007) Reproductive toxicity evaluation of a new camptothecin anticancer agent, CKD-602, in pregnant/lactating female rats and their offspring. Cancer Chemother Pharmacol 59:383–395

    Article  PubMed  CAS  Google Scholar 

  • Dalal RP, Goldfarb DS (2011) Melamine-related kidney stones and renal toxicity. Nat Rev Nephrol 7:267–274

    Article  PubMed  CAS  Google Scholar 

  • de Kloet ER, Oitzl MS, Joels M (1999) Stress and cognition: are corticosteroids good or bad guys? Trends Neurosci 22:422–426

    Article  PubMed  Google Scholar 

  • D’Hooge R, De Deyn PP (2001) Applications of the Morris water maze in the study of learning and memory. Brain Res Rev 36:60–90

    Article  PubMed  Google Scholar 

  • Dobson RL, Motlagh S, Quijano M, Cambron RT, Baker TR, Pullen AM, Regg BT, Bigalow-Kern AS, Vennard T, Fix A, Reimschuessel R, Overmann G, Shan Y, Daston GP (2008) Identification and characterization of toxicity of contaminants in pet food leading to an outbreak of renal toxicity in cats and dogs. Toxicol Sci 106:251–262

    Article  PubMed  CAS  Google Scholar 

  • Dudai Y (2004) The neurobiology of consolidations, or, how stable is the engram? Ann Rev Psychol 55:51–86

    Article  Google Scholar 

  • Florian C, Roullet P (2004) Hippocampal CA3-region is crucial for acquisition and memory consolidation in Morris water maze task in mice. Behav Brain Res 154:365–374

    Article  PubMed  Google Scholar 

  • Gil-Mohapel J, Boehme F, Patten A, Cox A, Kainer L, Giles E, Brocardo PS, Christie BR (2011) Altered adult hippocampal neuronal maturation in a rat model of fetal alcohol syndrome. Brain Res 1384:29–41

    Article  PubMed  CAS  Google Scholar 

  • Goodlett CR, Johnson TB (1997) Neonatal binge ethanol exposure using intubation: timing and dose effects on place learning. Neurotoxicol Teratol 19:435–446

    Article  PubMed  CAS  Google Scholar 

  • Gossner CM, Schlundt J, Ben Embarek P, Hird S, Lo-Fo-Wong D, Beltran JJ, Teoh KN, Tritscher A (2009) The melamine incident: implications for international food and feed safety. Environ Health Perspect 117:1803–1808

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Graziano A, Petrosini L, Bartoletti A (2003) Automatic recognition of explorative strategies in the Morris water maze. J Neurosci Methods 130:33–44

    Article  PubMed  Google Scholar 

  • Han G, An L, Yang B, Si L, Zhang T (2014) Nicotine-induced impairments of spatial cognition and long-term potentiation in adolescent male rats. Hum Exp Toxicol 33:203–213

    Article  PubMed  CAS  Google Scholar 

  • Hau AK, Kwan TH, Li PK (2009) Melamine toxicity and the kidney. J Am Soc Nephrol 20:245–250

    Article  PubMed  CAS  Google Scholar 

  • Jingbin W, Ndong M, Kai H, Matsuno K, Kayama F (2010) Placental transfer of melamine and its effects on rat dams and fetuses. Food Chem Toxicol 48:1791–1795

    Article  PubMed  CAS  Google Scholar 

  • Kim SH, Lee IC, Lim JH, Shin IS, Moon C, Park SC, Kim HC, Kim JC (2011) Effects of melamine on pregnant dams and embryo-fetal development in rats. J Appl Toxicol 31:506–514

    Article  PubMed  CAS  Google Scholar 

  • Lee I, Kesner RP (2002) Differential contribution of NMDA receptors in hippocampal subregions to spatial working memory. Nat Neurosci 5:162–168

    Article  PubMed  CAS  Google Scholar 

  • Mast RW, Jeffcoat AR, Sadler BM, Kraska RC, Friedman MA (1983) Metabolism, disposition and excretion of [14C]melamine in male Fischer 344 rats. Food Chem Toxicol 21:807–810

    Article  PubMed  CAS  Google Scholar 

  • McEwen BS (1999) Stress and hippocampal plasticity. Ann Rev Neurosci 22:105–122

    Article  PubMed  CAS  Google Scholar 

  • Savvaki M, Theodorakis K, Zoupi L, Stamatakis A, Tivodar S, Kyriacou K, Stylianopoulou F, Karagogeos D (2010) The expression of TAG-1 in glial cells is sufficient for the formation of the juxtaparanodal complex and the phenotypic rescue of tag-1 homozygous mutants in the CNS. J Neurosci 30:13943–13954

    Article  PubMed  CAS  Google Scholar 

  • Schaefer TL, Vorhees CV, Williams MT (2009) Mouse plasmacytoma-expressed transcript 1 knock out induced 5-HT disruption results in a lack of cognitive deficits and an anxiety phenotype complicated by hypoactivity and defensiveness. Neuroscience 164:1431–1443

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Suzuki S, Toledo-Pereyra LH, Rodriguez FJ, Cejalvo D (1993) Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine. Transplantation 55:1265–1272

    Article  PubMed  CAS  Google Scholar 

  • Takeda K, Jin MB, Fujita M, Fukai M, Sakurai T, Nakayama M, Taniguchi M, Suzuki T, Shimamura T, Furukawa H, Todo S (2003) A novel inhibitor of Rho-associated protein kinase, Y-27632, ameliorates hepatic ischemia and reperfusion injury in rats. Surgery 133:197–206

    Article  PubMed  Google Scholar 

  • Tang Y, Zucker RS (1997) Mitochondrial involvement in post-tetanic potentiation of synaptic transmission. Neuron 18:483–491

    Article  PubMed  CAS  Google Scholar 

  • Toescu EC, Vreugdenhil M (2010) Calcium and normal brain ageing. Cell Calcium 47:158–164

    Article  PubMed  CAS  Google Scholar 

  • Tyan YC, Yang MH, Jong SB, Wang CK, Shiea J (2009) Melamine contamination. Anal Bioanal Chem 395:729–735

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Liu F, Wei Y, Liu D (2011) The effect of exogenous melamine on rat hippocampal neurons. Toxicol Ind Health 27:571–576

    Article  PubMed  Google Scholar 

  • Whitlock JR, Heynen AJ, Shuler MG, Bear MF (2006) Learning induces long-term potentiation in the hippocampus. Science 313:1093–1097

    Article  PubMed  CAS  Google Scholar 

  • Wu LG, Saggau P (1994) Presynaptic calcium is increased during normal synaptic transmission and paired-pulse facilitation, but not in long-term potentiation in area CA1 of hippocampus. J Neurosci 14:645–654

    PubMed  CAS  Google Scholar 

  • Wu YT, Huang CM, Lin CC, Ho WA, Lin LC, Chiu TF, Tarng DC, Lin CH, Tsai TH (2009) Determination of melamine in rat plasma, liver, kidney, spleen, bladder and brain by liquid chromatography-tandem mass spectrometry. J Chromatogr A 1216:7595–7601

    Article  PubMed  CAS  Google Scholar 

  • Yang J, An L, Yao Y, Yang Z, Zhang T (2011) Melamine impairs spatial cognition and hippocampal synaptic plasticity by presynaptic inhibition of glutamatergic transmission in infant rats. Toxicology 289:167–174

    Article  PubMed  CAS  Google Scholar 

  • Yang Y, Xiong GJ, Yu DF, Cao J, Wang LP, Xu L, Mao RR (2012) Acute low-dose melamine affects hippocampal synaptic plasticity and behavior in rats. Toxicol Lett 214:63–68

    Article  PubMed  CAS  Google Scholar 

  • Zagron G, Weinstock M (2006) Maternal adrenal hormone secretion mediates behavioural alterations induced by prenatal stress in male and female rats. Behav Brain Res 175:323–328

    Article  PubMed  CAS  Google Scholar 

  • Zucker RS, Regehr WG (2002) Short-term synaptic plasticity. Annu Rev Physiol 64:355–405

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (31171053, 11232005) and 111 Project (B08011).

Author contributions

TZ and LA conceived and designed the experiments; LA performed the experiments and analyzed the data; LA and TZwrote the manuscript. Two authors approved the final version for publication.

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Authors and Affiliations

  1. College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, People’s Republic of China

    Lei An & Tao Zhang

  2. Department of Physiology, University of Saskatchewan, Saskatoon, S7N 5E5, Canada

    Lei An

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  1. Lei An
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  2. Tao Zhang
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Correspondence to Lei An or Tao Zhang.

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An, L., Zhang, T. Comparison Impairments of Spatial Cognition and Hippocampal Synaptic Plasticity Between Prenatal and Postnatal Melamine Exposure in Male Adult Rats. Neurotox Res 29, 218–229 (2016). https://doi.org/10.1007/s12640-015-9578-0

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  • DOI: https://doi.org/10.1007/s12640-015-9578-0

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