title: Chronic dietary exposure to chlorpyrifos causes behavioral impairments, low activity of brain membrane-bound acetylcholinesterase, and increased brain acetylcholinesterase-R mRNA.
abstract: Chlorpyrifos (CPF) is an organophosphate (OP) insecticide that is metabolically activated to the highly toxic chlorpyrifos oxon. Dietary exposure is the main route of intoxication for non-occupational exposures. However, only limited behavioral effects of chronic dietary exposure have been investigated. Therefore, male Wistar rats were fed a dose of 5mg/kg/day of CPF for thirty-one weeks. Animals were evaluated in spatial learning and impulsivity tasks after 21 weeks of CPF dietary exposure and one week after exposure ended, respectively. In addition, the degree of inhibition of brain acetylcholinesterase (AChE) was evaluated for both the soluble and particulate forms of the enzyme, as well as AChE gene expression. Also, brain acylpeptide hydrolase (APH) was investigated as an alternative target for OP-mediated effects. All variables were evaluated at various time points in response to CPF diet and after exposure ended. Results from behavioral procedures suggest cognitive and emotional disorders. Moreover, low levels of activity representing membrane-bound oligomeric forms (tetramers) were also observed. In addition, increased brain AChE-R mRNA levels were detected after four weeks of CPF dietary exposure. However, no changes in levels of brain APH were observed among groups. In conclusion, our data point to a relationship between cognitive impairments and changes in AChE forms, specifically to a high inhibition of the particulate form and a modification of alternative splicing of mRNA during CPF dietary exposure.
authors.affiliation: Departamento de Psicología, Universidad de Almería, Campus de Excelencia Internacional Agroalimentario CeiA3, La Cañada, 04120, Almería, Spain.
authors.forename: Caridad
authors.initials: C
authors.lastname: López-Granero
authors.forename: Diana
authors.initials: D
authors.lastname: Cardona
authors.forename: Estela
authors.initials: E
authors.lastname: Giménez
authors.forename: Rafael
authors.initials: R
authors.lastname: Lozano
authors.forename: José
authors.initials: J
authors.lastname: Barril
authors.forename: Fernando
authors.initials: F
authors.lastname: Sánchez-Santed
authors.forename: Fernando
authors.initials: F
authors.lastname: Cañadas
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D004390:Chlorpyrifos / Q000008:administration & dosage / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D004032:Diet / Q000009:adverse effects*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D007175:Impulsive Behavior / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002800:Cholinesterase Inhibitors; D012333:RNA, Messenger; D000110:Acetylcholinesterase; D004390:Chlorpyrifos