Comparative study on short- and long-term behavioral consequences of organophosphate exposure: Relationship to AChE mRNA expression

Caridad López-Granero, Diana Cardona, Estela Giménez, Rafael Lozano, José Barril, Michael Aschner, Fernando Sánchez-Santed, Fernando Cañadas

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Organophosphates (OPs) affect behavior by inhibiting acetylcholinesterase (AChE). While the cognitive short-term effects may be directly attributed to this inhibition, the mechanisms that underlie OP's long-term cognitive effects remain controversial and poorly understood. Accordingly, two experiments were designed to assess the effects of OPs on cognition, and to ascertain whether both the short- and long-term effects of are AChE-dependent. A single subcutaneous dose of 250. mg/kg chlorpyrifos (CPF), 1.5. mg/kg diisopropylphosphorofluoridate (DFP) or 15. mg/kg parathion (PTN) was administered to male Wistar rats. Spatial learning was evaluated 72. h or 23 weeks after exposure, and impulsive choice was tested at 10 and 30 weeks following OPs administration (experiment 1 and 2, respectively). Brain soluble and membrane-bound AChE activity, synaptic AChE-S mRNA, read-through AChE-R mRNA and brain acylpeptide hydrolase (APH) activity (as alternative non-cholinergic target) were analyzed upon completion of the behavioral testing (17 and 37 weeks after OPs exposure). Both short- and long-term CPF treatment caused statistically significant effects on spatial learning, while PTN treatment led only to statistically significant short-term effects. Neither CPF, DFP nor PTN affected the long-term impulsivity response. Long-term exposure to CPF and DFP significantly decreased AChE-S and AChE-R mRNA, while in the PTN treated group only AChE-S mRNA levels were decreased. However, after long-term OP exposure, soluble and membrane-bound AChE activity was indistinguishable from controls. Finally, no changes were noted in brain APH activity in response to OP treatment. Taken together, this study demonstrates long-term effects of OPs on AChE-S and AChE-R mRNA in the absence of changes in AChE soluble and membrane-bound activity. Thus, changes in AChE mRNA expression imply non-catalytic properties of the AChE enzyme.

Original languageEnglish (US)
Pages (from-to)57-64
Number of pages8
JournalNeuroToxicology
Volume40
DOIs
StatePublished - Jan 2014

Keywords

  • Acylpeptide hydrolase
  • Impulsive choice
  • Organophosphates
  • Read-through AChE, Synaptic AChE
  • Spatial learning

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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