title: Methamidophos exposure during the early postnatal period of mice: immediate and late-emergent effects on the cholinergic and serotonergic systems and behavior.
abstract: Organophosphates (OPs) are among the most used pesticides. Although some OPs have had their use progressively more restricted, other OPs are being used without sufficient investigation of their effects. Here, we investigated the immediate neurochemical and delayed neurochemical and behavioral actions of the OP methamidophos to verify whether there are concerns regarding exposure during early postnatal development. From the third to the nineth postnatal day (PN), Swiss mice were sc injected with methamidophos (1mg/kg). At PN10, we assessed cholinergic and serotonergic biomarkers in the cerebral cortex and brainstem. From PN60 to PN63, mice were submitted to a battery of behavioral tests and subsequently to biochemical analyses. At PN10, the effects were restricted to females and to the cholinergic system: Methamidophos promoted increased choline transporter binding in the brainstem. At PN63, in the brainstem, there was a decrease in choline transporter, a female-only decrease in 5HT1A and a male-only increase in 5HT2 receptor binding. In the cortex, choline acetyltransferase activity was decreased and 5HT2 receptor binding was increased both in males and females. Methamidophos elicited behavioral alterations, suggestive of increased depressive-like behavior and impaired decision making. There were no significant alterations on anxiety-related measures and on memory/learning. Methamidophos elicited cholinergic and serotonergic alterations that depended on brain region, sex, and age of the animals. These outcomes, together with the behavioral effects, indicate that this OP is deleterious to the developing brain and that alterations are indeed identified long after the end of exposure.
authors.affiliation: Departamento de Ciências Fisiológicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Carla S
authors.initials: CS
authors.lastname: Lima
authors.forename: Ana C
authors.initials: AC
authors.lastname: Dutra-Tavares
authors.forename: Fernanda
authors.initials: F
authors.lastname: Nunes
authors.forename: André L
authors.initials: AL
authors.lastname: Nunes-Freitas
authors.forename: Anderson
authors.initials: A
authors.lastname: Ribeiro-Carvalho
authors.forename: Cláudio C
authors.initials: CC
authors.lastname: Filgueiras
authors.forename: Alex C
authors.initials: AC
authors.lastname: Manhães
authors.forename: Armando
authors.initials: A
authors.lastname: Meyer
authors.forename: Yael
authors.initials: Y
authors.lastname: Abreu-Villaça
mesh_terms: D000375:Aging / Q000187:drug effects / Q000523:psychology; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D002794:Choline / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D007306:Insecticides; D026901:Membrane Transport Proteins; D009946:Organothiophosphorus Compounds; D011985:Receptors, Serotonin; C065637:choline transporter; D012701:Serotonin; C014655:methamidophos; D002794:Choline
keywords: AChE; ChAT; depression; development.; mood disorders; organophosphate; serotonin