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Long-term and low-dose malathion exposure causes cognitive impairment in adult mice: evidence of hippocampal mitochondrial dysfunction, astrogliosis and apoptotic events

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Abstract

The organophosphorus (OP) pesticide malathion is a neurotoxic compound whose acute toxicity is primarily caused by the inhibition of acetylcholinesterase (AChE), leading to cholinergic syndrome-related symptoms. Some lines of evidence indicate that long-term exposure to low levels of OP may produce neuropsychiatric and/or neurobehavioral signs that do not necessarily involve the AChE inhibition. This study evaluated the effects of a repeated (15-day period) and low-dose malathion exposure on spatial memory and discrimination (object location task), as well as on biochemical parameters in the hippocampus of mice [AChE and mitochondrial chain complexes activities; levels of proapoptotic proteins (Bax and Bak) and cholinergic neuronal and astroglial markers (ChAT and GFAP, respectively)]. Malathion treatments (30 and 100 mg/kg, s.c.) did not affect the body weight of animals and caused no evident signs of cholinergic toxicity throughout the treatment, although the highest dose (100 mg/kg) was associated with inhibition of AChE activity. Malathion-exposed animals showed a significant impairment on spatial memory and discrimination, which was correlated with a decrease in the mitochondrial complex I activity in the hippocampus. Moreover, malathion increased the levels of proapoptotic proteins and induced astroglial activation. The results show that long-term malathion exposure, at a dose that does not affect hippocampal AChE activity (30 mg/kg), caused impaired spatial memory and discrimination in mice that was related to hippocampal mitochondrial dysfunctional, astrogliosis and apoptosis. When extrapolated to humans, such results shed light on noncholinergic mechanisms likely related to the neurobehavioral and cognitive deficits observed in individuals chronically exposed to this pesticide.

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References

  • Abdel-Rahman A, Dechkovskaia AM, Goldstein LB, Bullman SH, Khan W, El-Masry EM, Abou-Donia MB (2004) Neurological deficits induced by malathion, DEET, and permethrin, alone or in combination in adult rats. J Toxicol Environ Health 67:331–356

    Article  CAS  Google Scholar 

  • Amr MM, Halim ZS, Moussa SS (1997) Psychiatric disorders among Egyptian pesticide applicators and formulators. Environ Res 73:193–199

    Article  CAS  PubMed  Google Scholar 

  • Angoa-Perez M, Kreipke CW, Thomas DM, Van Shura KE, Lyman M, McDonough JH, Kuhn DM (2010) Soman increases neuronal COX-2 levels: possible link between seizures and protracted neuronal damage. Neurotoxicology 31:738–746

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Assini FL, Duzzioni M, Takahashi RN (2009) Object location memory in mice: pharmacological validation and further evidence of hippocampal CA1 participation. Behav Brain Res 204:206–211

    Article  CAS  PubMed  Google Scholar 

  • Baille-Le Crom V et al (1995) Early regional changes of GFAP mRNA in rat hippocampus and dentate gyrus during soman-induced seizures. Neuroreport 7:365–369

    CAS  PubMed  Google Scholar 

  • Bajgar J (2004) Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv Clin Chem 38:151–216

    Article  CAS  PubMed  Google Scholar 

  • Banks CN, Lein PJ (2012) A review of experimental evidence linking neurotoxic organophosphorus compounds and inflammation. Neurotoxicology 33:575–584

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bartling A, Worek F, Szinicz L, Thiermann H (2007) Enzyme-kinetic investigation of different sarin analogues reacting with human acetylcholinesterase and butyrylcholinesterase. Toxicology 233:166–172

    Article  CAS  PubMed  Google Scholar 

  • Binukumar BK, Bal A, Kandimalla RJ, Gill KD (2010) Nigrostriatal neuronal death following chronic dichlorvos exposure: crosstalk between mitochondrial impairments, alpha synuclein aggregation, oxidative damage and behavioral changes. Mol Brain 3:35

    CAS  PubMed  Google Scholar 

  • Blasko I, Stampfer-Kountchev M, Robatscher P, Veerhuis R, Eikelenboom P, Grubeck-Loebenstein B (2004) How chronic inflammation can affect the brain and support the development of Alzheimer’s disease in old age: the role of microglia and astrocytes. Aging Cell 3:169–176

    Article  CAS  PubMed  Google Scholar 

  • Bosma H, van Boxtel MP, Ponds RW, Houx PJ, Jolles J (2000) Pesticide exposure and risk of mild cognitive dysfunction. Lancet 356:912–913

    Article  CAS  PubMed  Google Scholar 

  • Broadbent NJ, Gaskin S, Squire LR, Clark RE (2010) Object recognition memory and the rodent hippocampus. Learn Mem 17:5–11

    Article  PubMed Central  PubMed  Google Scholar 

  • Brocardo PS et al (2007) Zinc attenuates malathion-induced depressant-like behavior and confers neuroprotection in the rat brain. Toxicol Sci 97:140–148

    Article  CAS  PubMed  Google Scholar 

  • Brown MA, Brix KA (1998) Review of health consequences from high-, intermediate- and low-level exposure to organophosphorus nerve agents. J Appl Toxicol 18:393–408

    Article  CAS  PubMed  Google Scholar 

  • Buckley NA, Roberts D, Eddleston M (2004) Overcoming apathy in research on organophosphate poisoning. BMJ 329:1231–1233

    Article  PubMed Central  PubMed  Google Scholar 

  • Campana AD, Sanchez F, Gamboa C, Gomez-Villalobos Mde J, De La Cruz F, Zamudio S, Flores G (2008) Dendritic morphology on neurons from prefrontal cortex, hippocampus, and nucleus accumbens is altered in adult male mice exposed to repeated low dose of malathion. Synapse 62:283–290

    Article  CAS  PubMed  Google Scholar 

  • Cassina A, Radi R (1996) Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 328:309–316

    Article  CAS  PubMed  Google Scholar 

  • Chambers JE, Levi PE (1992) Organophosphates: chemistry, fate and effects. Academic Press Inc, San Diego, p 443

    Google Scholar 

  • Chen Y (2012) Organophosphate-induced brain damage: mechanisms, neuropsychiatric and neurological consequences, and potential therapeutic strategies. Neurotoxicology 33:391–400

    Article  CAS  PubMed  Google Scholar 

  • Collombet JM et al (2005) Soman poisoning increases neural progenitor proliferation and induces long-term glial activation in mouse brain. Toxicology 208:319–334

    Article  CAS  PubMed  Google Scholar 

  • Colosio C, Tiramani M, Brambilla G, Colombi A, Moretto A (2009) Neurobehavioural effects of pesticides with special focus on organophosphorus compounds: which is the real size of the problem? Neurotoxicology 30:1155–1161

    Article  CAS  PubMed  Google Scholar 

  • Costa LG (2006) Current issues in organophosphate toxicology. Clin Chim Acta 366:1–13

    Article  CAS  PubMed  Google Scholar 

  • Costa LG, Schwab BW, Murphy SD (1982) Tolerance to anticholinesterase compounds in mammals. Toxicology 25:79–97

    Article  CAS  PubMed  Google Scholar 

  • Daniell W, Barnhart S, Demers P, Costa LG, Eaton DL, Miller M, Rosenstock L (1992) Neuropsychological performance among agricultural pesticide applicators. Environ Res 59:217–228

    Article  CAS  PubMed  Google Scholar 

  • Dassanayake T, Weerasinghe V, Dangahadeniya U, Kularatne K, Dawson A, Karalliedde L, Senanayake N (2008) Long-term event-related potential changes following organophosphorus insecticide poisoning. Clin Neurophysiol 119:144–150

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Delgado EH, Streck EL, Quevedo JL, Dal-Pizzol F (2006) Mitochondrial respiratory dysfunction and oxidative stress after chronic malathion exposure. Neurochem Res 31:1021–1025

    Article  CAS  PubMed  Google Scholar 

  • Dewson G, Kluck RM (2009) Mechanisms by which Bak and Bax permeabilise mitochondria during apoptosis. J Cell Sci 122:2801–2808

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Di Filippo M, Chiasserini D, Tozzi A, Picconi B, Calabresi P (2010) Mitochondria and the link between neuroinflammation and neurodegeneration. J Alzheimers Dis 20(Suppl 2):S369–S379

    PubMed  Google Scholar 

  • Donaldson D, Kiely T, Grube A (2002) Pesticides industry sales and usage: 1998 and 1999 market estimates, U.S. EPA. Office of Pesticide Programs 14–15

  • Eikelenboom P, Rozemuller JM, van Muiswinkel FL (1998) Inflammation and Alzheimer’s disease: relationships between pathogenic mechanisms and clinical expression. Exp Neurol 154:89–98

    Article  CAS  PubMed  Google Scholar 

  • Ellison CA, Smith JN, Lein PJ, Olson JR (2011) Pharmacokinetics and pharmacodynamics of chlorpyrifos in adult male Long-Evans rats following repeated subcutaneous exposure to chlorpyrifos. Toxicology 287:137–144

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  CAS  PubMed  Google Scholar 

  • Farahat TM, Abdelrasoul GM, Amr MM, Shebl MM, Farahat FM, Anger WK (2003) Neurobehavioural effects among workers occupationally exposed to organophosphorous pesticides. Occup Environ Med 60:279–286

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fischer JC et al (1985) Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 153:23–36

    Article  CAS  PubMed  Google Scholar 

  • Hetz C et al (2005) Bax channel inhibitors prevent mitochondrion-mediated apoptosis and protect neurons in a model of global brain ischemia. J Biol Chem 280:42960–42970

    Article  CAS  PubMed  Google Scholar 

  • Jamal GA, Hansen S, Julu PO (2002) Low level exposures to organophosphorus esters may cause neurotoxicity. Toxicology 181–182:23–33

    Article  PubMed  Google Scholar 

  • Jurewicz J, Hanke W (2008) Prenatal and childhood exposure to pesticides and neurobehavioral development: review of epidemiological studies. Int J Occup Med Environ Health 21:121–132

    Article  PubMed  Google Scholar 

  • Kamel F, Hoppin JA (2004) Association of pesticide exposure with neurologic dysfunction and disease. Environ Health Perspect 112:950–958

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Krejci E, y Valenzuela IMP, Ameziane R, Akaaboune M (2006) Acetylcholinesterase dynamics at the neuromuscular junction of live animals. J Biol Chem 281:10347–10354

    Article  CAS  PubMed  Google Scholar 

  • Kwong TC (2002) Organophosphate pesticides: biochemistry and clinical toxicology. Ther Drug Monit 24:144–149

    Article  CAS  PubMed  Google Scholar 

  • Latini A et al (2005) Mitochondrial energy metabolism is markedly impaired by D-2-hydroxyglutaric acid in rat tissues. Mol Genet Metab 86:188–199

    Article  CAS  PubMed  Google Scholar 

  • Lim KL, Tay A, Nadarajah VD, Mitra NK (2011) The effect of consequent exposure of stress and dermal application of low doses of chlorpyrifos on the expression of glial fibrillary acidic protein in the hippocampus of adult mice. J Occup Med Toxicol (London, England)

  • Lockridge O, Duysen EG, Voelker T, Thompson CM, Schopfer LM (2005) Life without acetylcholinesterase: the implications of cholinesterase inhibition toxicity in AChE-knockout mice. Environ Toxicol Pharmacol 19:463–469

    Article  CAS  PubMed  Google Scholar 

  • Lotti M, Moretto A (2005) Organophosphate-induced delayed polyneuropathy. Toxicol Rev 24:37–49

    Article  CAS  PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  • Manthripragada AD, Costello S, Cockburn MG, Bronstein JM, Ritz B (2010) Paraoxonase 1, agricultural organophosphate exposure, and Parkinson disease. Epidemiology (Cambridge, Mass) 21:87–94

    Article  Google Scholar 

  • Maroni M, Colosio C, Ferioli A, Fait A (2000) Biological monitoring of pesticide exposure: a review. Introduction. Toxicology 143:1–118

    Article  CAS  PubMed  Google Scholar 

  • Masoud L, Vijayasarathy C, Fernandez-Cabezudo M, Petroianu G, Saleh AM (2003) Effect of malathion on apoptosis of murine L929 fibroblasts: a possible mechanism for toxicity in low dose exposure. Toxicology 185:89–102

    Article  CAS  PubMed  Google Scholar 

  • McDowell I, Hill G, Lindsay J, Helliwell B, Costa L, Beattie L et al (1994) The Canadian study of health and aging: risk factors for Alzheimer’s disease in Canada. Neurology 44:2073–2080

    Article  Google Scholar 

  • Mense SM et al (2006) The common insecticides cyfluthrin and chlorpyrifos alter the expression of a subset of genes with diverse functions in primary human astrocytes. Toxicol Sci 93:125–135

    Article  CAS  PubMed  Google Scholar 

  • Moser VC (1995) Comparisons of the acute effects of cholinesterase inhibitors using a neurobehavioral screening battery in rats. Neurotoxicol Teratol 17:617–625

    Article  CAS  PubMed  Google Scholar 

  • Murai T, Okuda S, Tanaka T, Ohta H (2007) Characteristics of object location memory in mice: behavioral and pharmacological studies. Physiol Behav 90:116–124

    Article  CAS  PubMed  Google Scholar 

  • Nelson LM (1995–1996) Epidemiology of ALS. Clin Neurosci 3:327–331

  • Nordberg A (2001) Nicotinic receptor abnormalities of Alzheimer’s disease: therapeutic implications. Biol Psychiatry 49:200–210

    Article  CAS  PubMed  Google Scholar 

  • Pope CN (1999) Organophosphorus pesticides: do they all have the same mechanism of action? J Toxicol Environ Health Part B 2:161–181

    Article  CAS  Google Scholar 

  • Prendergast MA, Terry AV, Buccafusco JJ (1997) Chronic, low-level exposure to diisopropylfluorophosphate causes protracted impairment of spatial navigation learning. Psychopharmacology 129:183–191

    Article  CAS  PubMed  Google Scholar 

  • Rauh VA et al (2006) Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children. Pediatrics 118:e1845–e1859

    Article  PubMed Central  PubMed  Google Scholar 

  • Ray DE, Richards PG (2001) The potential for toxic effects of chronic, low-dose exposure to organophosphates. Toxicol Lett 120:343–351

    Article  CAS  PubMed  Google Scholar 

  • Reddy PH, Beal MF (2008) Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer’s disease. Trends Mol Med 14:45–53

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rodgers K, Xiong S (1997a) Contributions of inflammatory mast cell mediators to alterations in macrophage function after malathion administration. Int J Immunopharmacol 19:149–156

    Article  CAS  PubMed  Google Scholar 

  • Rodgers K, Xiong S (1997b) Effect of administration of malathion for 14 days on macrophage function and mast cell degranulation. Fundam Appl Toxicol 37:95–99

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues L et al (2010) Treadmill training restores spatial cognitive deficits and neurochemical alterations in the hippocampus of rats submitted to an intracerebroventricular administration of streptozotocin. J Neural Transm 117:1295–1305

    Article  CAS  PubMed  Google Scholar 

  • Rohlman DS, Lasarev M, Anger WK, Scherer J, Stupfel J, McCauley L (2007) Neurobehavioral performance of adult and adolescent agricultural workers. Neurotoxicology 28:374–380

    Article  PubMed  Google Scholar 

  • Roldan-Tapia L, Parron T, Sanchez-Santed F (2005) Neuropsychological effects of long-term exposure to organophosphate pesticides. Neurotoxicol Teratol 27:259–266

    Article  CAS  PubMed  Google Scholar 

  • Rosenstock L, Keifer M, Daniell WE, McConnell R, Claypoole K (1991) Chronic central nervous system effects of acute organophosphate pesticide intoxication. Pestic Health Eff Study Group Lancet 338:223–227

    CAS  Google Scholar 

  • Rothlein J, Rohlman D, Lasarev M, Phillips J, Muniz J, McCauley L (2006) Organophosphate pesticide exposure and neurobehavioral performance in agricultural and non-agricultural Hispanic workers. Environ Health Perspect 114:691–696

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Russell RW, Overstreet DH (1987) Mechanisms underlying sensitivity to organophosphorus anticholinesterase compounds. Prog Neurobiol 28:97–129

    Article  CAS  PubMed  Google Scholar 

  • Rustin P, Chretien D, Bourgeron T, Gerard B, Rotig A, Saudubray JM, Munnich A (1994) Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 228:35–51

    Article  CAS  PubMed  Google Scholar 

  • Rusyniak DE, Nanagas KA (2004) Organophosphate poisoning. Semin Neurol 24:197–204

    Article  PubMed  Google Scholar 

  • Saleh AM, Vijayasarathy C, Masoud L, Kumar L, Shahin A, Kambal A (2003) Paraoxon induces apoptosis in EL4 cells via activation of mitochondrial pathways. Toxicol Appl Pharmacol 190:47–57

    Article  CAS  PubMed  Google Scholar 

  • Salvi RM, Lara DR, Ghisolfi ES, Portela LV, Dias RD, Souza DO (2003) Neuropsychiatric evaluation in subjects chronically exposed to organophosphate pesticides. Toxicol Sci 72:267–271

    Article  CAS  PubMed  Google Scholar 

  • Santos DB et al (2012) Probucol, a lipid-lowering drug, prevents cognitive and hippocampal synaptic impairments induced by amyloid beta peptide in mice. Exp Neurol 233:767–775

    Article  CAS  PubMed  Google Scholar 

  • Schapira AH (2010) Complex I: inhibitors, inhibition and neurodegeneration. Exp Neurol 224:331–335

    Article  CAS  PubMed  Google Scholar 

  • Sheridan C, Delivani P, Cullen SP, Martin SJ (2008) Bax- or Bak-induced mitochondrial fission can be uncoupled from cytochrome C release. Mol Cell 31:570–585

    Article  CAS  PubMed  Google Scholar 

  • Singh AK, Jiang Y (2003) Lipopolysaccharide (LPS) induced activation of the immune system in control rats and rats chronically exposed to a low level of the organothiophosphate insecticide, acephate. Toxicol Ind Health 19:93–108

    Article  CAS  PubMed  Google Scholar 

  • Singh S, Sharma N (2000) Neurological syndromes following organophosphate poisoning. Neurol India 48:308–313

    CAS  PubMed  Google Scholar 

  • Speed HE, Blaiss CA, Kim A, Haws ME, Melvin NR, Jennings M et al (2012) Delayed reduction of hippocampal synaptic transmission and spines following exposure to repeated subclinical doses of organophosphorus pesticide in adult mice. Toxicol Sci 125:196–208

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Steenland K, Jenkins B, Ames RG, O’Malley M, Chrislip D, Russo J (1994) Chronic neurological sequelae to organophosphate pesticide poisoning. Am J Public Health 84:731–736

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stephens R, Spurgeon A, Calvert IA, Beach J, Levy LS, Berry H, Harrington JM (1995) Neuropsychological effects of long-term exposure to organophosphates in sheep dip. Lancet 345:1135–1139

    Article  CAS  PubMed  Google Scholar 

  • Sungurtekin H, Gurses E, Balci C (2006) Evaluation of several clinical scoring tools in organophosphate poisoned patients. Clin Toxicol (Philadelphia, Pa) 44:121–126

    Article  Google Scholar 

  • Taylor P, Radic Z, Hosea NA, Camp S, Marchot P, Berman HA (1995) Structural bases for the specificity of cholinesterase catalysis and inhibition. Toxicol Lett 82–83:453–458

    Article  PubMed  Google Scholar 

  • Terry AV Jr (2012) Functional consequences of repeated organophosphate exposure: potential non-cholinergic mechanisms. Pharmacol Ther 134:355–365

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Terry AV Jr, Stone JD, Buccafusco JJ, Sickles DW, Sood A, Prendergast MA (2003) Repeated exposures to subthreshold doses of chlorpyrifos in rats: hippocampal damage, impaired axonal transport, and deficits in spatial learning. J Pharmacol Exp Ther 305:375–384

    Article  CAS  PubMed  Google Scholar 

  • Terry AV Jr et al (2007) Chronic, intermittent exposure to chlorpyrifos in rats: protracted effects on axonal transport, neurotrophin receptors, cholinergic markers, and information processing. J Pharmacol Exp Ther 322:1117–1128

    Article  CAS  PubMed  Google Scholar 

  • Valvassori SS et al (2007) Acute and subacute exposure to malathion impairs aversive but not non-associative memory in rats. Neurotox Res 12:71–79

    Article  CAS  PubMed  Google Scholar 

  • Whitton PS (2007) Inflammation as a causative factor in the aetiology of Parkinson’s disease. Br J Pharmacol 150:963–976

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zimmer LA, Ennis M, Shipley MT (1997) Soman-induced seizures rapidly activate astrocytes and microglia in discrete brain regions. J Comp Neurol 378:482–492

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The financial supports by (i) FINEP Research Grant “Rede Instituto Brasileiro de Neurociência (IBN-Net)”# 01.06.0842-00, (ii) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), (iii) Fundação de Apoio à Pesquisa do Estado de Santa Catarina (FAPESC-TO 1346/2010-3), (iv) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and (v) INCT-CNPq-Excitotoxicity and Neuroprotection are gratefully acknowledged. The project CNPq-PVE (300966/2014-8), afforded by CNPq and CAPES, is specially acknowledged.

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The authors declare that there are no conflict of interest.

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  1. Departamento de Bioquímica, Centro de Ciências Biológicas, Campus Universitário, Trindade, Bloco C, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, CEP 88040-900, Brazil

    Alessandra Antunes dos Santos, Aline Aita Naime, Jade de Oliveira, Dirleise Colle, Danúbia Bonfanti dos Santos, Mariana Appel Hort, Eduardo Luiz Gasnhar Moreira, Andreza Fabro de Bem & Marcelo Farina

  2. Institut d’Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (IIBB-CSIC), IDIBAPS, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain

    Cristina Suñol

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  1. Alessandra Antunes dos Santos
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  2. Aline Aita Naime
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Correspondence to Alessandra Antunes dos Santos or Marcelo Farina.

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dos Santos, A.A., Naime, A.A., de Oliveira, J. et al. Long-term and low-dose malathion exposure causes cognitive impairment in adult mice: evidence of hippocampal mitochondrial dysfunction, astrogliosis and apoptotic events. Arch Toxicol 90, 647–660 (2016). https://doi.org/10.1007/s00204-015-1466-0

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