TY - JOUR
T1 - Comparative study on short- and long-term behavioral consequences of organophosphate exposure
T2 - Relationship to AChE mRNA expression
AU - López-Granero, Caridad
AU - Cardona, Diana
AU - Giménez, Estela
AU - Lozano, Rafael
AU - Barril, José
AU - Aschner, Michael
AU - Sánchez-Santed, Fernando
AU - Cañadas, Fernando
N1 - Funding Information:
This work was supported by GV07/158 from the Conselleria d’Empresa, Universitat i Ciència–Generalitat Valenciana , PS09-01163 from FIS, Spain , PSI2011-26237 from MICINN , Spain, and from FEDER EU funds.
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
KW - Acylpeptide hydrolase
KW - Impulsive choice
KW - Organophosphates
KW - Read-through AChE, Synaptic AChE
KW - Spatial learning
UR - http://www.scopus.com/inward/record.url?scp=84890021412&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84890021412&partnerID=8YFLogxK
U2 - 10.1016/j.neuro.2013.11.004
DO - 10.1016/j.neuro.2013.11.004
M3 - Article
C2 - 24291005
AN - SCOPUS:84890021412
SN - 0161-813X
VL - 40
SP - 57
EP - 64
JO - Neurotoxicology
JF - Neurotoxicology
ER -