Skip to main content

Advertisement

Log in

Sex Differences and Effects of Estrogenic Compounds on the Expression of Inflammatory Molecules by Astrocytes Exposed to the Insecticide Dimethoate

  • Original Article
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

A low dose of the organophosphorus insecticide dimethoate (DMT) produces oxidation of lipids and proteins and impairs mitochondrial function in the brain of male rats, together with a reduction of gonadal hormones in plasma. Here, we have assessed whether DMT affected the expression of inflammatory molecules, the production of reactive oxygen species (ROS), and the expression of steroidogenic proteins and estrogen receptors in cortical astrocyte-enriched cultures obtained separately from male and female CD1 mice pups. Furthermore, we have analyzed whether estradiol may counteract the effects of DMT. A dose of DMT (2 μg/mL) did not affect cell viability, increased interleukin (IL) 6, IL1β, tumor necrosis factor (TNF)α, interferon-γ-inducible protein 10 (IP10), ERβ, steroidogenic acute regulatory protein, and aromatase mRNA levels and ERα protein levels in male but not in female cultures. Estradiol decreased the mRNA levels of IL6, IP10, TNFα, and IL1β in male but not in female cultures treated with DMT. The effect of estradiol was prevented by the ER antagonist ICI 182,780, fully imitated by an ERβ agonist and partially imitated by an ERα agonist. Furthermore, DMT increased the production of ROS in male astrocytes while estradiol reduced ROS production to control levels. These findings indicate that a sublethal dose of DMT alters astrocyte function. The selective action of estradiol on male astrocytes and the sexually dimorphic action of DMT suggest that the pesticide may have different neurological outcomes in males and females.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Agostinho P, Cunha RA, Oliveira C (2010) Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer’s disease. Curr Pharm Des 16:2766–2778

    Article  CAS  PubMed  Google Scholar 

  • Al-Bader MD, El-Abdallah AA, Redzic ZB (2008) Ontogenic profile of estrogen receptor alpha and beta mRNA and protein expression in fetal rat brain. Neurosci Lett 440:222–226

    Article  CAS  PubMed  Google Scholar 

  • Albensi BC, Mattson MP (2000) Evidence for the involvement of TNF and NF-κB in hippocampal synaptic plasticity. Synapse 35:151–159

    Article  CAS  PubMed  Google Scholar 

  • Amitai G, Adani R, Fishbein E, Meshulam H, Laish I, Dachir S (2006) Bifunctional compounds eliciting anti-inflammatory and anti-cholinesterase activity as potential treatment of nerve and blister chemical agents poisoning. J Appl Toxicol 26:81–87

    Article  CAS  PubMed  Google Scholar 

  • Arevalo MA, Santos-Galindo M, Bellini MJ, Azcoitia I, García-Segura LM (2010) Action of estrogens on glial cells: implication for neuroprotection. Biochim Biophys Acta 75:1106–1112

    Article  Google Scholar 

  • Arnold AP (2009) The organizational-activational hypothesis as the foundation for a unified theory of sexual differentiation of all mammalian tissues. Horm Behav 55:570–578

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Arnold S, Victor MB, Beyer C (2012) Estrogen and the regulation of mitochondrial structure and function in the brain. J Steroid Biochem Mol Biol 131:2–9

    Article  CAS  PubMed  Google Scholar 

  • Astiz M, de Alaniz MJT, Marra CA (2009a) Antioxidant defense system in rats simultaneously intoxicated with pesticides. Environ Toxicol Pharmacol 28:465–473

    Article  CAS  PubMed  Google Scholar 

  • Astiz M, de Alaniz MJT, Marra CA (2009b) Effect of pesticides on cell survival in liver and brain rat tissues. Ecotoxicol Environ Safe 72:2025–2032

    Article  CAS  Google Scholar 

  • Astiz M, de Alaniz MJT, Marra CA (2009c) The impact of simultaneous intoxication with agrochemicals on the antioxidant defense system in rats. Pestic Biochem Physiol 94:93–99

    Article  CAS  Google Scholar 

  • Astiz M, Hurtado de Catalfo GE, de Alaniz MJ, Marra CA (2009d) Involvement of lipids in dimethoate-induced inhibition of testosterone biosynthesis in rat interstitial cells. Lipids 44:703–718

    Article  CAS  PubMed  Google Scholar 

  • Astiz M, Arnal N, de Alaniz MJ, Marra CA (2011) Occupational exposure characterization in professional sprayers: clinical utility of oxidative stress biomarkers. Environ Toxicol Pharmacol 32:249–258

    Article  CAS  PubMed  Google Scholar 

  • Astiz M, Diz-Chaves Y, Garcia-Segura LM (2013) Sub-chronic exposure to the insecticide dimethoate induces a proinflammatory status and enhances the neuroinflammatory response to bacterial lipopolysaccharide in the hippocampus and striatum of male mice. Toxicol Appl Pharmacol. doi:10.1016/j.taap.2013.07.008

  • Azcoitia I, Arevalo MA, De Nicola AF, Garcia-Segura LM (2011) Neuroprotective actions of estradiol revisited. Trends Endocrinol Metab 22:467–473

    Article  CAS  PubMed  Google Scholar 

  • Bailek M, Zaremba P, Borowicz KK, Czuczwar SJ (2004) Neuroprotective role of testosterone in the nervous system. Pol J Pharmacol 56:509–518

    Google Scholar 

  • Bains M, Cousins JC, Roberts JL (2007) Neuroprotection by estrogen against MPP+-induced dopamine neuron death is mediated by ERα in primary cultures of mouse mesencephalon. Exp Neurol 204:767–776

    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  CAS  PubMed Central  PubMed  Google Scholar 

  • Bellini MJ, Hereñú CB, Goya RG, Garcia-Segura LM (2011) Insulin-like growth factor-I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide. J Neuroinflamm 8:21

    Article  CAS  Google Scholar 

  • Ben Abdallah F, Fetoui H, Zribi N, Fakfakh F, Ammar-Keskes L (2012) Antioxidant supplementations in vitro improve rat sperm parameters and enhance antioxidant enzyme activities against dimethoate-induced sperm damages. Andrologia 44(Suppl 1):272–279

    Article  PubMed  Google Scholar 

  • Brown CM, Suzuki S, Jelks KA, Wise PM (2009) Estradiol is a potent protective, restorative, and trophic factor after brain injury. Semin Reprod Med 27:240–249

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Brown CM, Mulcahey TA, Filipek NC, Wise PM (2010) Production of proinflammatory cytokines and chemokines during neuroinflammation: novel roles for estrogen receptors alpha and beta. Endocrinology 151:4916–4925

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bruce-Keller AJ, Keeling JL, Keller JN, Huang FF, Camondola S, Mattson MP (2000) Antiinflammatory effects of estrogen on microglial activation. Endocrinology 141:3646–3656

    CAS  PubMed  Google Scholar 

  • Buchanan MM, Hutchinson M, Watkins LR, Yin H (2010) Toll-like receptor 4 in CNS pathologies. J Neurochem 114:13–27

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cambron M, D’Haeseleer M, Laureys G, Clinckers R, Debruyne J, De Keyser J (2012) White-matter astrocytes, axonal energy metabolism, and axonal degeneration in multiple sclerosis. J Cereb Blood Flow Metab 32:413–424

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Campbell IL, Abraham CR, Masliah E, Kemper P, Inglis JD, Oldstone MBA, Mucke L (1993) Neurologic disease in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci USA 90:10061–10065

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Carbonaro V, Caraci F, Giuffrida ML, Merlo S, Canonico PL, Drago F, Copani A, Sortino MA (2009) Enhanced expression of ER alpha in astrocytes modifies the response of cortical neurons to β-Amiloid toxicity. Neurobiol Dis 33:415–421

    Article  CAS  PubMed  Google Scholar 

  • Carswell HV, Dominiczak AF, Garcia-Segura LM, Harada N, Hutchison JB, Macrae IM (2005) Brain aromatase expression after experimental stroke: topography and time course. J Steroid Biochem Mol Biol 96:89–91

    Article  CAS  PubMed  Google Scholar 

  • CASAFE (Cámara Argentina de Sanidad Agropecuaria y Fertilizantes) (2007) Guía de Productos Fitosanitarios para la República Argentina, 13th edn. CASAFE, Buenos Aires

    Google Scholar 

  • Casida JE, Quistad GB (2005) Serine hydrolase targets of organophosphorus toxicants. Chem Biol Interact 157:277–283

    Article  PubMed  Google Scholar 

  • Cerciat M, Unkila M, Garcia-Segura LM, Arevalo MA (2010) Selective estrogen receptor modulators decrease the production of interleukin-6 and interferon-γ-inducible protein-10 by astrocytes exposed to inflammatory challenge in vitro. Glia 58:93–102

    Article  CAS  PubMed  Google Scholar 

  • Chu I, Arnaout A, Loiseau S, Sun J, Seth A, McMahon C, Chun K, Hennessy B, Mills GB, Nawaz Z, Slingerland JM (2007) Src promotes estrogen-dependent estrogen receptor alpha proteolysis in human breast cancer. J Clin Invest 117:2205–2215

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Conejo NM, González-Pardo H, Cimadevilla JM, Argüelles JA, Díaz F, Vallejo-Seco G, Arias JL (2005) Influence of gonadal steroids on the glial fibrillary acidic protein-immunoreactive astrocyte population in young rat hippocampus. J Neurosci Res 79:488–494

    Article  CAS  PubMed  Google Scholar 

  • Dhandapani KM, Brann DW (2007) Role of astrocytes in estrogen-mediated neuroprotection. Exp Gerontol 42:70–75

    Article  CAS  PubMed  Google Scholar 

  • Di Monte D (2003) The environment and Parkinson′s disease: is the nigrostriatal system preferentially targeted by neurotoxins? Lancet Neurol 2:531–537

    Article  PubMed  Google Scholar 

  • Dubal DB, Rau SW, Shughrue PJ, Zhu H, Yu J, Cashion AB, Suzuki S, Gerhold LM, Bottner MB, Dubal SB, Merchanthaler I, Kindy MS, Wise PM (2006) Differential modulation of estrogen receptors (ERs) in ischemic brain injury: a role for ERalpha in estradiol-mediated protection against delayed cell death. Endocrinology 147:3076–3084

    Article  CAS  PubMed  Google Scholar 

  • Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD (2002) IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J Immunol 168:3195–3204

    CAS  PubMed  Google Scholar 

  • Dziedzic T (2006) Systemic inflammatory markers and risk of dementia. Am J Alzheimers Dis Other Demen 21:258–262

    Article  PubMed  Google Scholar 

  • Farber JM (1997) Mig and IP-10: CXC chemokines that target lymphocytes. J Leukoc Biol 61:246–257

    CAS  PubMed  Google Scholar 

  • Farina C, Aloisi F, Meinl E (2007) Astrocytes are active players in cerebral innate immunity. Trends Immunol 28:138–145

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Fernandez S, Almeida A, Bolaños J (2012) Antioxidant and bioenergetic coupling between neurons and astrocytes. Biochem J 443:3–12

    Article  CAS  PubMed  Google Scholar 

  • Fox EM, Davis RJ, Shupnik MA (2008) ERbeta in breast cancer: onlooker, passive player, or active protector? Steroids 73:1039–1051

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Garcia-Ovejero D, Veiga S, Garcia-Segura LM, Doncarlos LL (2002) Glial expression of estrogen and androgen receptors after rat brain injury. J Comp Neurol 50:256–271

    Article  Google Scholar 

  • Garcia-Ovejero D, Azcoitia I, Don Carlos LL, Melcangi RC, Garcia-Segura LM (2005) Glia-neuron cross-talk in the neuroprotective mechanism of sex steroid hormones. Brain Res Rev 48:273–286

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Segura LM (2008) Aromatase in the brain: not just for reproduction anymore. J Neuroendocrinol 20:705–712

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Segura LM, Suarez I, Segovia S, Tranque PA, Calés JM, Aguilera P, Olmos G, Guillamón A (1988) The distribution of glial fibrillary acidic protein in the adult rat brain is influenced by the neonatal levels of sex steroids. Brain Res 456:357–363

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Segura LM, Dueñas M, Busiguina S, Naftolin F, Chowen JA (1995) Gonadal hormone regulation of neuronal-glial interactions in the developing neuroendocrine hypothalamus. J Steroid Biochem Mol Biol 53:293–298

    Article  CAS  PubMed  Google Scholar 

  • Gargouri B, Mansour RB, Abdallah FB, Elfekih A, Lassoued S, Khaled H (2011) Protective effect of quercetin against oxidative stress caused by dimethoate in human peripheral blood lymphocytes. Lipids Health Dis 23:149–153

    Article  Google Scholar 

  • Guevara R, Gianotti M, Oliver J, Roca P (2011) Age and sex-related changes in rat brain mitochondrial oxidative status. Exp Gerontol 46:923–928

    Article  CAS  PubMed  Google Scholar 

  • Guo J, Duckles S, Weiss J, Li X, Krause D (2012) 17β-Estradiol prevents cell death and mitochondrial dysfunction by an estrogen receptor-dependent mechanism in astrocytes after oxygen-glucose deprivation/reperfusion. Free Radic Biol Med 52:2151–2160

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hald A, Lotharious J (2005) Oxidative stress and inflammation in Parkinson′s disease: is there a casual link? Exp Neurol 193:279–290

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B, Gutteridge JMC (1999) Free Radicals in Biology and Medicine, 3rd edn. Oxford University Press, Oxford

    Google Scholar 

  • Hargreaves AJ (2012) Neurodegenerations induced by organophosphorus compounds. Adv Exp Med Biol 724:189–204

    Article  CAS  PubMed  Google Scholar 

  • Horton MK, Kahn LG, Perera F, Barr DB, Rauh V (2012) Does the home environment and the sex of the child modify the adverse effects of prenatal exposure to chlorpyrifos on child working memory? Neurotoxicol Teratol 34:534–541

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kapka-Skrzypczak L, Cyranka M, Skrzypczak M, Kruszewski M (2011) Biomonitoring and biomarkers of organophosphate pesticides exposure-state of the art. Ann Agric Environ Med 18:294–303

    CAS  PubMed  Google Scholar 

  • Kim S, Steelman AJ, Koito H, Li J (2011) Astrocytes promote TNF-mediated toxicity to oligodendrocyte precursors. J Neurochem 116:53–66

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Koelle GB, Gilman A (1949) Anticholinesterase drugs. J Pharmacol Exp Ther 2:166–216

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Lavaque E, Mayen A, Azcoitia I, Tena-Sempere M, Garcia-Segura LM (2006) Sex differences, developmental changes, response to injury and cAMP regulation of the mRNA levels of steroidogenic acute regulatory protein, cytochrome p450scc, and aromatase in the olivocerebellar system. J Neurobiol 66:308–318

    Article  CAS  PubMed  Google Scholar 

  • Levin ED, Timofeeva OA, Yang L, Petro A, Ryde IT, Wrench N, Seidler FJ, Slotkin TA (2010) Early postnatal parathion exposure in rats causes sex-selective cognitive impairment and neurotransmitter defects which emerge in aging. Behav Brain Res 208:319–327

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lewis DK, Johnson AB, Stohlgren S, Harms A, Sohrabji F (2008) Effects of estrogen receptors agonist on regulation of the inflammatory response in astrocytes from young adult and middle-aged female rats. J Neuroimmunol 195:47–59

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li C, Zhao R, Gao K, Wei Z, Yin MY, Lau LT, Chui D, Hoi Yu AC (2011) Astrocytes: implications for neuroinflammatory pathogenesis of Alzheimer’s disease. Curr Alzheimer Res 8:67–80

    Article  PubMed  Google Scholar 

  • Liu B, Gao H-M, Hong J-S (2003) Parkinson’s disease and exposures to infectious agents and pesticides and the occurrence of brain injuries: role of neuroinflammation. Environ Health Perspect 111:1065–1073

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liu M, Hurn PD, Roselli CE, Alkayed NJ (2007) Role of P450 aromatase in sex specific astrocytic cell death. J Cereb Blood Flow Metab 27:135–141

    Article  CAS  PubMed  Google Scholar 

  • Loram LC, Sholar PW, Taylor FR, Wiesler JL, Babb JA, Strand KA, Berkelhammer D, Day HE, Maier SF, Watkins LR (2012) Sex and estradiol influence glial pro-inflammatory responses to lipopolysaccharide in rats. Psychoneuroendocrinology 37:1688–1699

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Losi G, Cammarota M, Carmignoto G (2012) The role of astroglia in the epileptic brain. Front Pharmacol 3:132

    Article  PubMed Central  PubMed  Google Scholar 

  • Mason JL, Suzuki K, Chaplin DD, Matsushima GK (2001) Interleukin-1beta promotes repair of the CNS. J Neurosci 21:7046–7051

    CAS  PubMed  Google Scholar 

  • Mong JA, Glaser E, McCarthy MM (1999) Gonadal steroids promote glial differentiation and alter neuronal morphology in the developing hypothalamus in a regionally specific manner. J Neurosci 19:1464–1472

    CAS  PubMed  Google Scholar 

  • Moreno JA, Streifel KM, Sullivan KA, Legare ME, Tjalkens RB (2009) Developmental exposure to manganese increases adult susceptibility to inflammatory activation of glia and neuronal protein nitration. Toxicol Sci 112:405–415

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mrak RE, Griffin WS (2005) Potential inflammatory biomarkers in Alzheimer’s disease. J Alzheimers Dis 8:369–375

    CAS  PubMed  Google Scholar 

  • Nikodemova M, Watters JJ (2011) Outbred ICR/CD1 mice display more severe neuroinflammation mediated by microglial TLR4/CD14 activation than inbred C57Bl/6 mice. Neuroscience 190:67–74

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pannu R, Barbosa E, Singh AK, Singh I (2005) Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats. J Neurosci Res 79:340–350

    Article  CAS  PubMed  Google Scholar 

  • Park KM, Bowers WJ (2010) Tumor necrosis factor-alpha mediated signaling in neuronal homeostasis and dysfunction. Cell Signal 22:977–983

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Parpura V, Heneka MT, Montana V, Oliet SH, Schousboe A, Haydon PG, Stout RF Jr, Spray DC, Reichenbach A, Pannicke T, Pekny M, Pekna M, Zorec R, Verkhratsky A (2012) Glial cells in (patho)physiology. J Neurochem 121:4–27

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Penkowa M, Giralt M, Lago N, Camats J, Carrasco J, Hernandez J, Molinero A, Campbell IL, Hidalgo J (2003) Astrocyte-targeted expression of IL-6 protects the CNS against a focal brain injury. Exp Neurol 181:130–148

    Article  CAS  PubMed  Google Scholar 

  • Quintana A, Molinero A, Borup R, Nielsen FC, Campbell IL, Penkowa M, Hidalgo J (2008) Effect of astrocyte-targeted production of IL-6 on traumatic brain injury and its impact on the cortical transcriptome. Dev Neurobiol 68:195–208

    Article  CAS  PubMed  Google Scholar 

  • Raber J, Sorg O, Horn TF, Yu N, Koob GF, Campbell IL, Bloom FE (1998) Inflammatory cytokines: putative regulators of neuronal and neuro-endocrine function. Brain Res Brain Res Rev 26:320–326

    Article  CAS  PubMed  Google Scholar 

  • Rauh VA, Perera FP, Horton MK, Whyatt RM, Bansal R, Hao X, Liu J, Barr DB, Slotkin TA, Peterson BS (2012) Brain anomalies in children exposed prenatally to a common organophosphate pesticide. Proc Natl Acad Sci USA 109:7871–7876

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Razmara A, Duckles SP, Krause DN, Procaccio V (2007) Estrogen suppresses brain mitochondrial oxidative stress in female and male rats. Brain Res 1176:71–81

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ritz MF, Hausmann ON (2008) Effect of 17β-Estradiol on functional outcome, release of cytokines, astrocyte reactivity and inflammatory spreading after spinal cord injury in male rats. Brain Res 1203:177–188

    Article  CAS  PubMed  Google Scholar 

  • Ritz B, Yu F (2000) Parkinson’s disease mortality and pesticide exposure in California. 1984–1994. Int J Epidemiol 29:323–329

    Article  CAS  PubMed  Google Scholar 

  • Rothwell N (2003) Interleukin-1 and neuronal injury: mechanisms, modification, and therapeutic potential. Brain Behav Immun 17:152–157

    Article  PubMed  Google Scholar 

  • Rush T, Liu XQ, Hjelmhaug J, Lobner D (2010) Mechanisms of chlorpyrifos and diazinon induced neurotoxicity in cortical culture. Neuroscience 166:899–906

    Article  CAS  PubMed  Google Scholar 

  • Saldanha CJ, Duncan KA, Walters BJ (2009) Neuroprotective actions of brain aromatase. Front Neuroendocrinol 30:106–118

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Santos-Galindo M, Acaz-Fonseca E, Bellini MJ, García-Segura LM (2011) Sex differences in the inflammatory response of primary astrocytes to lipopolysaccharide. Biol Sex Differ 11:2–7

    Google Scholar 

  • Schwarz JM, Bilbo SD (2012) Sex, glia and development: interactions in health and disease. Horm Behav 62:243–253

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Scott E, Zhang Q, Wang R, Vadlamudi R, Brann D (2012) Estrogen neuroprotection and the critical period hypothesis. Front Neuroendocrinol 33:85–104

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sidoryk-Wegrzynowicz M, Wegrzynowicz M, Lee E, Bowman AB, Aschner M (2011) Role of astrocytes in brain function and disease. Toxicol Pathol 39:115–123

    Article  PubMed  Google Scholar 

  • Simpkins JW, Don Yi K, Yang SH, Dykens JA (2010) Mitochondrial mechanisms of estrogen neuroprotection. Biochim Biophys Acta 1800:1113–1120

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Skoff AM, Zhao C, Adler JE (2009) Interleukin-1alpha regulates substance P expression and release in adult sensory neurons. Exp Neurol 217:395–400

    Article  CAS  PubMed  Google Scholar 

  • Soltaninejad K, Abdollahi M (2009) Current opinion on the science of organophosphate pesticides and toxic stress: a systematic review. Med Sci Monit 15:75–90

    Google Scholar 

  • Steele ML, Robinson SR (2012) Reactive astrocytes give neurons less support: implications for Alzheimer’s disease. Neurobiol Aging 33:423.e1–423.e13

    Article  CAS  Google Scholar 

  • Su Z, Yuan Y, Chen J, Zhu Y, Qiu Y, Zhu F, Huang A, He C (2011) Reactive astrocytes inhibit the survival and differentiation of oligodendrocyte precursor cells by secreted TNF-alpha. J Neurotrauma 28:1089–1100

    Article  PubMed  Google Scholar 

  • Sundar Boyalla S, Barbara Victor M, Roemgens A, Beyer C, Arnold S (2011) Sex- and brain region-specific role of cytochrome c oxidase in 1-methyl-4-phenylpyridinium-mediated astrocyte vulnerability. J Neurosci Res 89:2068–2082

    Article  CAS  PubMed  Google Scholar 

  • Sunkaria A, Wani WY, Sharma DR, Gill KD (2012) Dichlorvos exposure results in activation induced apoptotic cell death in primary rat microglia. Chem Res Toxicol 25:1762–1770

    Article  CAS  PubMed  Google Scholar 

  • Swartz KR, Liu F, Sewell D, Schochet T, Campbell I, Sandor M, Fabry Z (2001) Interleukin-6 promotes post-traumatic healing in the central nervous system. Brain Res 896:86–95

    Article  CAS  PubMed  Google Scholar 

  • Syed MM, Phulwani NK, Kielian T (2007) Tumor necrosis factor-alpha (TNF-alpha) regulates toll-like receptor 2 (TLR2) expression in microglia. J Neurochem 103:1461–1471

    Article  CAS  PubMed  Google Scholar 

  • Venerosi A, Ricceri L, Rungi A, Sanghez V, Calamandrei G (2010) Gestational exposure to the organophosphate chlorpyrifos alters social-emotional behaviour and impairs responsiveness to the serotonin transporter inhibitor fluvoxamine in mice. Psychopharmacology 208:99–107

    Article  CAS  PubMed  Google Scholar 

  • Venerosi A, Ricceri L, Tait S, Calamandrei G (2012) Sex dimorphic behaviors as markers of neuroendocrine disruption by environmental chemicals: the case of chlorpyrifos. Neurotoxicology 33:1420–1426

    Article  CAS  PubMed  Google Scholar 

  • Walsh LP, Webster DR, Stocco DM (2000) Dimethoate inhibits steroidogenesis by disrupting transcription of the steroidogenic acute regulatory (StAR) gene. J Endocrinol 167:253–263

    Article  CAS  PubMed  Google Scholar 

  • Worrall NK, Chang K, LeJeune WS, Misko TP, Sullivan PM, Ferguson TB, Williamson JR (1997) TNF-alpha causes reversible in vivo systemic vascular barrier dysfunction via NO-dependent and -independent mechanisms. Am J Physiol 273(Part 2):H2565–H2574

    CAS  PubMed  Google Scholar 

  • Zurich MG, Honegger P, Schilter B, Costa LG, Monnet-Tschudi F (2004) Involvement of glial cells in the neurotoxicity of parathion and chlorpyrifos. Toxicol Appl Pharmacol 201:97–104

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Maria García-Mauriño for excellent technical assistance and Dr. Maria L. de Ceballos for her help in cell viability assays. This study was supported by subprograma B para movilidad de jóvenes doctores en centros españoles, Ministerio de Educación Spain and by Ministerio de Economía y Competitividad, Spain, Grant Number BFU2011-30217-C03-01.

Conflict of interests

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mariana Astiz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Astiz, M., Acaz-Fonseca, E. & Garcia-Segura, L.M. Sex Differences and Effects of Estrogenic Compounds on the Expression of Inflammatory Molecules by Astrocytes Exposed to the Insecticide Dimethoate. Neurotox Res 25, 271–285 (2014). https://doi.org/10.1007/s12640-013-9417-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-013-9417-0

Keywords

Navigation