| Methyl parathion (O-O-dimethyl-O-p-nitrophenylphosphorothioate) is an organophosphorus (OP) compound that may only be applied as an agricultural pesticide. Interest in methyl parathion as a public health concern has increased with the recognition that it has been illegally used in private residences and businesses throughout the south and central United States. The acute toxic effects of OP are generally associated with the inhibition of acetylcholinesterase (ACNE), resulting in accumulation of acetylcholine (ACh) in central and peripheral synapses, and induction of hypercholinergic symptoms. Epidemiological studies provided evidence for a link between chronic exposure to OP insecticides and a variety of psychiatric sequelae including depression, apathy, irritability, and schizophrenia.; This investigation focus on the long-term CNS effects of methyl parathion exposure by using dosage regimen similar to that likely to have occurred in situations of human exposure to methyl parathion following indoor application. Young adult Sprague-Dawley male rats were injected daily with subcutaneous doses of methyl parathion for 21 days. Neurobehavioral assessments included body weight, water/food intake, tremors, motor activity, maximum speed on a rotating rod, and learning and retention of active shock avoidance.; Biochemical studies revealed a progressive and persistent inhibition of AChE activity in blood and brain regions. Furthermore, a down-regulation of muscarinic receptor subtypes among brain regions was observed using quantitative autoradiographic binding with [3H] pirenzepine, [3H] AD-FX384, and [3H]QNB to exam M1, M2 and total muscarinic receptor, respectively. The loss of cholinergic muscarinic receptors in critical regions is hypothesized to compromise higher brain functions. By correlating the results from neurochemical and behavioral studies, we suggest that the special sensitivity of muscarinic receptors in certain regions, such as basal ganglia, may relate to and explain a progressive deterioration of locomotor functions during repeated exposure to methyl parathion.; Most recently, real-time RT-PCR approach was employed to further investigate the effect of long-term exposure to methyl parathion on gene expression of muscarinic receptor subtypes and AChE. An increase in gene expression of m 2 subtype was detected frontal cortex and striatum following repeated exposure to methyl parathion. The increase in gene expression of a presynaptic autoreceptor, M2 subtype, could be a compensatory mechanism to inhibit further release of ACh upon persistent inhibition of AChE. This could be an additional mechanism underlying the development of tolerance to repeated methyl parathion exposure. |
