Influence of dermal exposure to the pyrethroid insecticide deltamethrin on rat brain microanatomy and cholinergic/dopaminergic neurochemistry.
Deltamethrin is a pesticide largely used. Acute toxicity of this compound was extensively investigated, whereas less information is available on the effects of subchronic and/or chronic exposure to deltamethrin or on the effects of its dermal absorption. Sparse data are also available on deltamethrin neurotoxicity. This study has assessed in the rat the effects of dermal application of deltamethrin (30 mg/kg/day in cyclohexane for 4 weeks to the skin of the back of the neck) on microanatomy of cerebrocortical areas (frontal cortex and hippocampus) and on cholinergic and dopaminergic neurotransmission markers. Treatment with deltamethrin caused nerve cell loss and the appearance of signs of neuronal sufferance primarily in layer III of frontal cortex as well as in the dentate gyrus and to a lesser extent in the CA1 and CA3 subfields of hippocampus. Deltamethrin induced also astrogliosis. Cholinergic neurotransmission markers investigated in frontal cortex, hippocampus and striatum were acetylcholine (ACh), the synthesizing and catabolic enzymes choline acetyltransferase and acetylcholinesterase and the high affinity ACh uptake system labeled with [(3)H]hemicholinium-3. These markers were unaffected by deltamethrin administration. Dopamine and the dopamine plasma membrane transporter labeled with [(3)H]GBR 12935 were unaffected by treatment with deltamethrin in frontal cortex and decreased significantly in hippocampus and striatum. These findings indicate that dermal exposure to the pyrethroid insecticide deltamethrin using an administration module mimicking a possible long-lasting occupational skin contact is accompanied by cerebrocortical injury and loss of hippocampal and striatal dopamine and dopamine transporter. The sensitivity of dopaminergic system in our experimental model suggests that dermal exposure to deltamethrin could represent a risk factor for Parkinson's disease.
Tayebati
Seyed Khosrow
SK
Department of Experimental Medicine and Public Health, University of Camerino, Italy. khosrow.tayebati@unicam.it
Di Tullio
Maria Antonietta
MA
Ricci
Alberto
A
Amenta
Francesco
F
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000123:Acetyltransferases / Q000378:metabolism; D000279:Administration, Cutaneous; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002853:Chromatography, Liquid; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007306:Insecticides / Q000008:administration & dosage; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009570:Nitriles / Q000008:administration & dosage*; D011722:Pyrethrins / Q000008:administration & dosage*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D009435:Synaptic Transmission / Q000187:drug effects*
D050483:Dopamine Plasma Membrane Transport Proteins; D005904:Glial Fibrillary Acidic Protein; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin; D000123:Acetyltransferases; D000110:Acetylcholinesterase; D000109:Acetylcholine; D004298:Dopamine