title: Spine density and dendritic branching pattern of hippocampal CA1 pyramidal neurons in neonatal rats chronically exposed to the organophosphate paraoxon.
abstract: The organophosphate cholinesterase (ChE) inhibitor paraoxon is the oxidized active metabolite of parathion, a pesticide whose use in agriculture has been matter of increasing concern. The present work was aimed at reproducing a prolonged exposure to low concentrations of paraoxon and assessing possible damage to the hippocampus during the period of most significant cholinergic development. Male Wistar rats were given, from P8 to P20, subcutaneous daily injections of paraoxon (0.1, 0.15 and 0.2mg/kg). The rate of body weight gain was reduced by all doses of paraoxon and brain ChE activity progressively decreased up to 60% by P21. Some deaths occurred in the beginning of the treatment, but the surviving animals showed neither convulsions nor overt signs of cholinergic hyperstimulation. Morphometric analysis of Lucifer Yellow-stained CA1 pyramidal neurons in coronal sections of the hippocampus showed that by P21 paraoxon caused a decrease in spine density on basal but not on secondary apical dendrites. The dendritic arborization and the pyramidal and granular cell body layers were not altered by paraoxon. ChE staining decreased in all hippocampal and dentate gyrus regions studied, whereas choline acetyltransferase (ChAT) and zinc-positive fibers remained as in control. In summary, chronic exposure to low paraoxon concentrations during the period of rapid brain development caused significant and selective decrease in basal dendritic spine density of the CA1 pyramidal neurons. Distinct modulation of the basal tree at the stratum oriens by the interplay of cholinergic afferent and GABAergic interneurons, as well as the remodeling process in response to a repetitive and rather mild paraoxon insult, may account for this selective susceptibility of basal dendritic spines. The hippocampal alterations described here occurred in the absence of toxic cholinergic signs and may affect brain development and cause functional deficits that could continue into adulthood.
authors.affiliation: Departament of Basic and Clinical Pharmacology and Institute of Biophysics Carlos Chagas Filho, Health Sciences Center, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-590, Brazil.
authors.forename: Hélio R
authors.initials: HR
authors.lastname: Santos
authors.forename: Wagner M
authors.initials: WM
authors.lastname: Cintra
authors.forename: Yasco
authors.initials: Y
authors.lastname: Aracava
authors.forename: Carla M
authors.initials: CM
authors.lastname: Maciel
authors.forename: Newton G
authors.initials: NG
authors.lastname: Castro
authors.forename: Edson X
authors.initials: EX
authors.lastname: Albuquerque
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000379:methods; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D007306:Insecticides / Q000008:administration & dosage*; D008297:Male; D010261:Paraoxon / Q000008:administration & dosage*; D017966:Pyramidal Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007306:Insecticides; D000110:Acetylcholinesterase; D010261:Paraoxon