The current study focused on the MMP2 and MMP9 expression in cerebral cortex and hippocampus of newborn mice under maternal lead exposure. Lead exposure was initiated from gestation to weaning. Lead acetate was dissolved in deionized water with concentration of 0.1, 0.2, and 0.5% and was absorbed through daily drinking. On day 21 after birth, lead in blood and tissue levels was examined by Graphite Furnace Atomic Absorption Spectrum (GFAAS). The protein expressions of MMP2 and MMP9 in hippocampus and cerebral cortex tissues were tested by western blotting and immunohistochemistry. Compared to the control group, blood, cerebral cortex, and hippocampus lead levels of newborn mice in 0.1, 0.2, and 0.5% lead exposure groups were markedly high (P < 0.05), and mice within the 0.2 and 0.5% lead exposure groups performed much worse than that of the control group in Water Maze test (P < 0.05). Compared with the control group, MMP2 and MMP9 expressions in hippocampus were up-regulated in the lead exposure groups (P < 0.05), and the MMP2 and MMP9 expressions in cerebral cortex were also higher (P < 0.05). The increased expression of MMP2 and MMP9 in the hippocampus and cerebral cortex may lead to the neurotoxicity in the context of maternal lead exposure.
SenutMCCingolaniPSenAKrugerAShaikAHirschHSuhrSTRudenD. Epigenetics of early-life lead exposure and effects on brain development. Epigenomics2012; 4: 665–74.
2.
JungSYKimSLeeKKimJYBaeWKLeeKHanJSKimS. Association between secondhand smoke exposure and blood lead and cadmium concentration in community dwelling women: the fifth Korea National Health and Nutrition Examination Survey (2010–2012). BMJ Open2015; 5: e008218–e008218.
3.
LiuMCLiuXQWangWShenXFCheHLGuoYYZhaoMGChenJYLuoWJ. Involvement of microglia activation in the lead induced long-term potentiation impairment. PLoS One2012; 7: e43924–e43924.
4.
García-LestónJRoma-TorresJMayanOSchroecksnadelSFuchsDMoreiraAOPásaroEMéndezJTeixeiraJPLaffonB. Assessment of immunotoxicity parameters in individuals occupationally exposed to lead. J Toxicol Environ Health A2012; 75: 807–18.
5.
SureshCDennisAOHeinzJVemuriMCChettyCS. Melatonin protection against lead-induced changes in human neruoblastoma cell cultures. Int J Toxicol2006; 25: 459–64.
6.
CanfieldRLHendersonCRJrCory-SlechtaDACoxCJuskoTALanphearBP. Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. N Engl J Med2003; 348: 1517–26.
7.
BunnTLParsonsPJKaoEDietertRR. Exposure to lead during critical windows of embryonic development: differential immunotoxic outcome based on stage of exposure and gender. Toxicol Sci2001; 64: 57–66.
8.
BergersGBrekkenRMcMahonGVuTHItohTTamakiKTanzawaKThorpePItoharaSWerbZHanahanD. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol2000; 2: 737–44.
9.
SolemanSFilippovMADityatevAFawcettJW. Targeting the neural extracellular matrix in neurological disorders. Neuroscience2013; 253: 194–213.
10.
ZuckerSCaoJ. Selective matrix metalloproteinase (MMP) inhibitors in cancer therapy: ready for prime time?Cancer Biol Ther2009; 8: 2371–3.
11.
VisseRNagaseH. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res2003; 92: 827–39.
12.
NagaseHVisseRMurphyG. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res2006; 69: 562–73.
13.
YongVWPowerCForsythPEdwardsDR. Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci2001; 2: 502–11.
14.
WrightJWHardingJW. The brain angiotensin system and extracellular matrix molecules in neural plasticity, learning, and memory. Prog Neurobiol2004; 72: 263–93.
15.
FatarMStroickMGriebeMHennericiM. Matrix metalloproteinases in cerebrovascular diseases. Cerebrovasc Dis2005; 20: 141–51.
16.
SzklarczykALapinskaJRylskiMMcKayRDKaczmarekL. Matrix metalloproteinase-9 undergoes expression and activation during dendritic remodeling in adult hippocampus. J Neurosci2002; 22: 920–30.
17.
KhuthSTAkaokaHPagenstecherAVerlaetenOBelinMFGiraudonPBernardA. Morbillivirus infection of the mouse central nervous system induces region-specific upregulation of MMPs and TIMPs correlated to inflammatory cytokine expression. J Virol2001; 75: 8268–82.
18.
HindmarchCYaoSGeightonGPatonJMurphyD. A comprehensive description of the transcriptome of the hypothalamoneurohypophyseal system in euhydrated and dehydrated rats. Proc Natl Acad Sci USA2006; 103: 1609–14.
19.
HuQFuHRenTWangSZhouWSongHHanYDongS. Maternal low-level lead exposure reduces the expression of PSA-NCAM and the activity of sialyltransferase in the hippocampi of neonatal rat pups. Neurotoxicology2008; 29: 675–81.
20.
Diaz-SanchezMWilliamsKDeLucaGCEsiriMM. Protein co-expression with axonal injury in multiple sclerosis plaques. Acta Neuropathol2006; 111: 289–99.
21.
OpdenakkerGNelissenIVan DammeJ. Functional roles and therapeutic targeting of gelatinase B and chemokines in multiple sclerosis. Lancet Neurol2003; 2: 747–56.
22.
AgrawalSAndersonPDurbeejMvan RooijenNIvarsFOpdenakkerGSorokinLM. Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis. J Exp Med2006; 203: 1007–19.
23.
ZhangX-YLiuA-PRuanD-YLiuJ. Effect of developmental lead exposure on the expression of specific NMDA recep tor subunit mRNAs in the hippocampus of neonatal rats by digoxigenin-labeled in situ hybridizati on histochemistry. Neurotoxicol Teratol2002; 24: 149–60.
24.
GilbertMELasleySM. Developmental lead (Pb) exposure reduces the ability of the NMDA antagonist MK-801 to suppress long-term potentiation (LTP) in the rat dentate gyrus, in vivo. Neurotoxicol Teratol2007; 29: 385–93.
25.
De MarcoMHalpernRBarrosHM. Early behavioral effects of lead perinatal exposure in rat pups. Toxicology2005; 211: 49–58.
26.
YunSWGärtnerUArendtTHoyerS. Increase in vulnerability of middle-aged rat brain to lead by cerebral energy depletion. Brain Res Bull2000; 52: 371–8.
27.
BuetersTvon EulerMBendelOvon EulerG. Degeneration of newly formed CA1 neurons following global ischemia in the rat. Exp Neurol2008; 209: 114–24.
28.
PrasanthiRPJReddyGHReddyGR. Calcium or zinc supplementation reduces lead toxicity: assessment of behavioral dysfunction in young and adult mice. Nutr Res2006; 26: 537–45.
29.
WangZ-FTangL-LYanHWangY-JTangX-C. Effects of huperzine A on memory deficits and neurotrophic factors production after transient cerebral ischemia and reperfusion in mice. Pharmacol Biochem Behav2006; 83: 603–11.
30.
Jaako-MovitsKZharkovskyTRomantchikOJurgensonMMerisaluEHeidmetsLTZharkovskyA. Developmental lead exposure impairs contextual fear conditioning and reduces adult hippocampal neurogenesis in the rat brain. Int J Dev Neurosci2005; 23: 627–35.
31.
JiangCWangJLiXLiuCChenNHaoY. Progesterone exerts neuroprotective effects by inhibiting inflammatory response after stroke. Inflamm Res2009; 58: 619–24.
32.
WenTLiuYCYangHWLiuHYLiuXDWangGJXieL. Effect of 21-day exposure of phenobarbital, carbamazepine and phenytoin on P-glycoprotein expression and activity in the rat brain. J Neurol Sci2008; 270: 99–106.
33.
NiggJTNikolasMMark KnottnerusGCavanaghKFridericiK. Confirmation and extension of association of blood lead with attention-deficit/hyperactivity disorder (ADHD) and ADHD symptom domains at population-typical exposure levels. J Child Psychol Psychiatry2010; 51: 58–65.
34.
SurkanPJZhangATrachtenbergFDanielDBMcKinlaySBellingerDC. Neuropsychological function in children with blood lead levels <10 microg/dL. Neurotoxicology2007; 28: 1170–7.
35.
MazumdarMBellingerDCGregasMAbanillaKBacicJNeedlemanHL. Low-level environmental lead exposure in childhood and adult intellectual function: a follow-up study. Environ Health2011; 10: 24–24.
36.
CecilKMBrubakerCJAdlerCMDietrichKNAltayeMEgelhoffJCWesselSElangovanIHornungRJarvisKLanphearBP. Decreased brain volume in adults with childhood lead exposure. PLoS Med2008; 5: e112–e112.
37.
YuanWHollandSKCecilKMDietrichKNWesselSDAltayeMHornungRWRisMDEgelhoffJCLanphearBP. The impact of early childhood lead exposure on brain organization: a functional magnetic resonance imaging study of language function. Pediatrics2006; 118: 971–7.
38.
Baranowska-BosiackaIGutowskaIRybickaMNowackiPChlubekD. Neurotoxicity of lead. Hypothetical molecular mechanisms of synaptic function disorders. Neurol Neurochir Pol2012; 46: 569–78.
39.
PlusquellecPMuckleGDewaillyEAyottePJacobsonSWJacobsonJL. The relation of low-level prenatal lead exposure to behavioral indicators of attention in Inuit infants in Arctic Quebec. Neurotoxicol Teratol2007; 29: 527–37.
40.
CottrellECSecklJR. Prenatal stress, glucocorticoids and the programming of adult disease. Front Behav Neurosci2009; 3: 19–19.
41.
SchneiderJSKiddSKAndersonDW. Influence of developmental lead exposure on expression of DNA methyltransferases and methyl cytosine-binding proteins in hippocampus. Toxicol Lett2013; 217: 75–81.
42.
GuZCuiJBrownSFridmanRMobasherySStronginAYLiptonSA. A highly specific inhibitor of matrix metalloproteinase-9 rescues laminin from proteolysis and neurons from apoptosis in transient focal cerebral ischemia. J Neurosci2005; 25: 6401–8.
43.
NobelLJDonovanFIgarashiTGoussevSWerbZ. Matrix metalloproteinases limit functional recovery alter spinal cord injury by modulation of early vascular events. J Neurosci2002; 22: 7526–35.
44.
LarsenPHWellsJEStallcupWBOpdenakkerGYongVW. Matrix metalloproteinase-9 facilitates remyelination in part by processing the inhibitory NG2 proteoglycan. J Neurosci2003; 23: 11127–35.
45.
ZhaoBQWangSKimHYStorrieHRosenBRMooneyDJWangXLoEH. Role of matrix metalloproteinases in delayed cortical responses after stroke. Nat Med2006; 12: 441–5.
46.
ShiryaevSASavinovAYCieplakPRatnikovBIMotamedchabokiKSmithJWStronginAY. Matrix metalloproteinase proteolysis of the myelin basic protein isoforms is a source of immunogenic peptides in autoimmune multiple sclerosis. PLoS One2009; 4: e4952–e4952.
47.
MirshafieyAAsghariBGhalamfarsaGJadidi-NiaraghFAziziG. The significance of matrix metalloproteinases in the immunopathogenesis and treatment of multiple sclerosis. Sultan Qaboos Univ Med J2014; 14: e13–25.
48.
NewmanTAWoolleySTHughesPMSibsonNRAnthonyDCPerryVH. T-cell- and macrophage-mediated axon damage in the absence of a CNS-specific immune response: involvement of metalloproteinases. Brain2001; 124: 2203–14.
49.
LuLTonchevABKaplamadzhievDBBonevaNBMoriYSaharaSMaDNakayaMAKikuchiMYamashimaT. Expression of matrix metalloproteinases in the neurogenic niche of the adult monkey hippocampus after ischemia. Hippocampus2008; 18: 1074–84.
50.
KoyamaYTanakaK. Intracerebroventricular administration of an endothelin ET(B)-receptor agonist increases expression of matrix metalloproteinase-2 and -9 in rat brain. J Pharmacol Sci2010; 114: 433–43.
51.
TongWChenWOstrowskiRPMaQSouvenirRZhangLZhangJHTangJ. Maternal hypoxia increases the activity of MMPs and decreases the expression of TIMPs in the brain of neonatal rats. Dev Neurobiol2010; 70: 182–94.
52.
KawasakiYXuZZWangXParkJYZhuangZYTanPHGaoYJRoyKCorfasGLoEHJiRR. Distinct roles of matrix metalloproteases in the early-and late-phase development of neuropathic pain. Nat Med2008; 14: 331–6.
53.
LindbergRLDe GrootCJMontagneLFreitagPvan der ValkPKapposLLeppertD. The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis. Brain2001; 124: 1743–53.
