Spine Density and Dendritic Branching Pattern of Hippocampal CA1 Pyramidal Neurons in Neonatal Rats Chronically Exposed to the Organophosphate Paraoxon
Section snippets
INTRODUCTION
Paraoxon, a powerful organophosphate (OP) cholinesterase (ChE) inhibitor, is the oxidized metabolite of parathion, one of the most acutely toxic pesticides registered by the US Environmental Protection Agency (EPA) and used worldwide. Parathion is readily absorbed through the skin and mucosal membranes and, according to reports from World Health Organization it represents the number one cause of occupational and accidental intoxication and fatalities among the pesticides (FAO, 2003).
Most of the
Experimental Animals
Male Wistar rats were maintained in a 12 h light/dark cycle with access to food and water ad libitum. Paraoxon (90% purity, Sigma, St. Louis, MO, USA) was dissolved in peanut oil and dilutions were made such that 1 μl/g body weight was administered. Three doses of paraoxon (0.1, 0.15 or 0.2 mg/kg) were tested. Pups received daily, from P8 to P20, subcutaneous injections of paraoxon, and morphometric analyses were performed at P21. In one set of experiments, animals were exposed to paraoxon up to
Body Development and Mortality
Male pups were injected daily with 0.1, 0.15 or 0.2 mg/kg body weight paraoxon from P8 to P20, a time during which significant brain cholinergic development and synaptogenesis are known to occur. At P8, there was no significant difference in body weight between the control and treated groups (ANOVA, P>0.11), but the rate of animal growth was progressively reduced during the 13-day period of paraoxon treatment at all doses tested (Fig. 1). A trend of increased loss at higher doses could be seen,
DISCUSSION
The present study was aimed at analyzing the effects of daily exposure of newborn rats from P8 to P20 to low doses of paraoxon (0.1–0.2 mg/kg) on hippocampal cytoarchitecture and on morphometric characteristics of the CA1 pyramidal neurons that may be correlated with the main cholinergic markers, ChE and ChAT, during a period when the brain cholinergic system undergoes significant development. Although paraoxon produced a reduction in the rate of body weight gain, diminished the whole brain ChE
Acknowledgements
This work was supported by US Army Medical Research and Development Command contract DAMD-17-95-C-5063; USPHS Grant NS41671; FUJB/UFRJ, CNPq, FAPERJ, PRONEX/Brazil. We are especially grateful to Ms. Mabel Zelle for her expert technical assistance.
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