title: Long-term and low-dose malathion exposure causes cognitive impairment in adult mice: evidence of hippocampal mitochondrial dysfunction, astrogliosis and apoptotic events.
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.
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Campus Universitário, Trindade, Bloco C, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, CEP 88040-900, Brazil. alessandraantunes@hotmail.com.
authors.forename: Alessandra Antunes
authors.initials: AA
authors.lastname: dos Santos
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Campus Universitário, Trindade, Bloco C, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, CEP 88040-900, Brazil.
authors.forename: Aline Aita
authors.initials: AA
authors.lastname: Naime
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Campus Universitário, Trindade, Bloco C, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, CEP 88040-900, Brazil.
authors.forename: Jade
authors.initials: J
authors.lastname: de Oliveira
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Campus Universitário, Trindade, Bloco C, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, CEP 88040-900, Brazil.
authors.forename: Dirleise
authors.initials: D
authors.lastname: Colle
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Campus Universitário, Trindade, Bloco C, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, CEP 88040-900, Brazil.
authors.forename: Danúbia Bonfanti
authors.initials: DB
authors.lastname: dos Santos
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Campus Universitário, Trindade, Bloco C, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, CEP 88040-900, Brazil.
authors.forename: Mariana Appel
authors.initials: MA
authors.lastname: Hort
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Campus Universitário, Trindade, Bloco C, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, CEP 88040-900, Brazil.
authors.forename: Eduardo Luiz Gasnhar
authors.initials: EL
authors.lastname: Moreira
authors.affiliation: Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (IIBB-CSIC), IDIBAPS, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Suñol
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Campus Universitário, Trindade, Bloco C, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, CEP 88040-900, Brazil.
authors.forename: Andreza Fabro
authors.initials: AF
authors.lastname: de Bem
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Campus Universitário, Trindade, Bloco C, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, CEP 88040-900, Brazil. marcelo.farina@ufsc.br.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D003072:Cognition Disorders / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007306:Insecticides / Q000633:toxicity*; D008294:Malathion / Q000633:toxicity*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D065852:Spatial Memory / Q000187:drug effects; D036401:Toxicity Tests, Chronic / Q000379:methods
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D008294:Malathion
keywords: Chronic exposure; Cognitive impairment; Malathion; Mice; Organophosphorus pesticides