Chlorpyrifos is an organophosphorus insecticide that elicits acute toxicity through inhibition of acetylcholinesterase (AChE), leading to acetylcholine accumulation and prolonged stimulation of cholinergic receptors throughout the central and peripheral nervous systems. Previous studies have indicated that neurodevelopment may also be impaired through alternative pathways, including reduction of cyclic adenosine monophosphate (cAMP)-catalyzed downstream events. The upstream initiating events that underlie noncholinergic neurological actions of chlorpyrifos and other organophosphorus compounds remain unclear. To investigate the potential role of fatty acid signaling disruption as a mechanism of toxicity, lipid metabolism and fatty acid profiles were examined to identify alterations that may play a critical role in upstream signaling in the central nervous system (CNS). Juvenile rainbow trout were treated for 7 days with nominal chlorpyrifos concentrations previously reported to diminish olfactory responses (10, 20, and 40 μg/l). Although lethality was noted higher in doses, measured chlorpyrifos concentrations of 1.38 μg/l (nominal concentration 10 μg/l) significantly reduced the activity of AChE and two serine lipases, monoacylglycerol lipase, and fatty acid amide hydrolase in the brain. Reductions in lysophosphatidylethanolamines (16:0, 18:0, 18:1, and 22:6) derived from the phosphatidylethanolamines and free fatty acids (palmitic acid 16:0, linolenic acid 18:3, eicosadienoic acid 20:2, arachidonic acid 20:4, and docosahexaenoic acid 22:6) were also noted, suggesting that chlorpyrifos inhibited the metabolism of select phospholipid signaling precursors at sublethal concentrations. These results indicate that in addition to AChE inhibition, environmentally relevant chlorpyrifos exposure alters serine lipase activity and lipid metabolites in the trout brain, which may compromise neuronal signaling and impact neurobehavioral responses in aquatic animals.

Background Aluminum is the third most prevalent element in the earth’s crust. In most conditions, it is tightly bound to form inaccessible compounds, however in low soil pH, the ionized form of aluminum can be taken up by plant roots and distributed throughout the plant tissue. Following this uptake, nectar and pollen concentrations in low soil pH regions can reach nearly 300 mg/kg. Inhibition of acetylcholinesterase (AChE) has been demonstrated following aluminum exposure in mammal and aquatic invertebrate species. In honey bees, behaviors consistent with AChE inhibition have been previously recorded; however, the physiological mechanism has not been tested, nor has aversive conditioning. Results This article presents results of ingested aqueous aluminum chloride exposure on AChE as well as acute exposure effects on aversive conditioning in an Apis mellifera ligustica hive. Contrary to previous findings, AChE activity significantly increased as compared to controls following exposure to 300 mg/L Al3+. In aversive conditioning studies, using an automated shuttlebox, there were time and dose-dependent effects on learning and reduced movement following 75 and 300 mg/L exposures. Conclusions These findings, in comparison to previous studies, suggest that aluminum toxicity in honey bees may depend on exposure period, subspecies, and study metrics. Further studies are encouraged at the moderate-high exposure concentrations as there may be multiple variables that affect toxicity which should be teased apart further.

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The single residue mutation of butyrylcholinesterase (BChEG117H) hydrolyzes a number of organophosphosphorus (OP) anticholinesterases. Whereas other BChE active site/proximal mutations have been investigated, none are sufficiently active to be prophylactically useful. In a fundamentally different computer simulations driven strategy, we identified a surface peptide loop (residues 278–285) exhibiting dynamic motions during catalysis and modified it via residue insertions. We evaluated these loop mutants using computer simulations, substrate kinetics, resistance to inhibition, and enzyme reactivation assays using both the choline ester and OP substrates. A slight but significant increase in reactivation was noted with paraoxon with one of the mutants, and changes in K M and catalytic efficiency were noted in others. Simulations suggested weaker interactions between OP versus choline substrates and the active site of all engineered versions of the enzyme. The results indicate that an improvement of OP anticholinesterase hydrolysis through surface loop engineering may be a more effective strategy in an enzyme with higher intrinsic OP compound hydrolase activity.

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