Cortical excitatory amino acid system alterations play key role in cognitive action after 90-day administration of dimethoate in rats

Introduction
Chronic exposure to organophosphorus pesticides plays a role in development of neurobehavioral disorders, in which excitatory amino acid system(EAAs) help explain the symptoms in addition to the well-characterized AChE inhibition.

Methods
In present study, we investigated the role of excitatory amino acid system(EAAs) in neurobehavioral alteration and mRNA expression of Microtubule associated protein 2 (MAP-2), Neuron specific enolase (NSE), Glial fibrillary acidic protein (GFAP) and Calcium-binding protein S100β after subchronic exposure (90days by gavage 5 times/weekly ) to dimethoate (i5, 10, or 20mg/kg•bw) in rats. MAP-2, NSE, GFAP and S100β are brain-specific proteins, abnormal mRNA expression of which hints neuron and astrocytes’ injury.

Results
Studies reported that these brain-specific proteins can also be influenced by organophosphorus pesticide. MK801, antagonist of NMDAR, plays therapeutic role in preventing and alleviating seizure, epilepsy induced by organophosphorus pesticide. Our results demonstrated that after 90 days of repeated oral exposure to dimethoate, concentration of excitatory amino acid (Asperate and Glutamate) decreased, along with increases in mRNA level of four brain-specific proteins in rat cortex;Meanwhile rats learning and spatial memory was impaired. When rats were pretreated with MK801, the result showed increases in concentration of both excitatory amino acids and decreases in mRNA levels of four brain-specific proteins along with improved learning and spatial memory.

Discussion
These results suggest that cortical EAAs involve in regulation of cognitive action, and glutamate may play a role in vivo in controling neuronal and astrocytic response to injury and introduces the possibility that brain injury-induced gliosis may be pharmacologically manipulated by MK801.