Developmental deltamethrin: Sex-specific hippocampal effects in Sprague Dawley rats

• Published in: Current research in toxicology Vol. 3; p. 100093
• Main Authors: Pitzer, Emily M., Sugimoto, Chiho, Regan, Samantha L., Gudelsky, Gary A., Williams, Michael T., Vorhees, Charles V.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-01-2022; Elsevier
• Subjects: Apoptosis; Caspase-3; Cytokines; Deltamethrin; Dopamine; from the special issue PMC Invite 2021-2022; Glutamate; Long-term potentiation; Pyrethroids; Rats; Dopamine; Cytokines; DLM; Long-term potentiation; Pyrethroids; Rats; LTP; Glutamate; Deltamethrin; Caspase-3; DA; Apoptosis; DA, dopamine; DLM, deltamethrin; LTP, Long-term potentiation
• ISSN: 2666-027X; 2666-027X
• DOI: 10.1016/j.crtox.2022.100093

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•Low dose deltamethrin (DLM) effects have been reported in developing rodents.•Rats treated with DLM from P3-20 showed effects on NMDA-NR2A and NMDA-NR2B.•DLM increased apoptosis in the dentate gyrus by TUNEL staining.•DLM altered hippocampal long-term potentiation (LTP).•DLM has multiple long-term effects on rat brain after early exposure.
Pyrethroid pesticides are widely used and can cause long-term effects after early exposure. Epidemiological and animal studies reveal associations between pyrethroid exposure and altered cognition following prenatal and/or neonatal exposure. However, little is known about the cellular effects of such exposure. Sprague Dawley rats were gavaged with 0 or 1.0 mg/kg deltamethrin (DLM), a Type II pyrethroid, in corn oil (dose volume 5 mL/kg) once per day from postnatal day (P) 3–20 and assessed shortly after dosing ended or as adults. No effects of DLM exposure were found on striatal dopaminergic markers, nor on AMPA receptor subunits or on NMDA-NR1. However, DLM increased NMDA-NR2A and decreased NMDA-NR2B levels in the hippocampus, in males but not females. Additionally, adult hippocampal CA1 long-term potentiation was increased in DLM-treated males but not females. Potassium stimulated extracellular glutamate release in the hippocampus was not affected using in vivo microdialysis. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) showed increased apoptotic cells in the dentate gyrus of male rats, in the absence of changes in cleaved caspase-3 at P21. Proinflammatory cytokines interferon gamma trended up in striatum, interleukin-1β trended down in nucleus accumbens, IL-13 trended up in hippocampus, and keratinocyte chemoattractant/human growth-regulated oncogene (KC/GRO or CXCL1) was significantly increased in the hippocampus in male DLM-treated rats on P20. The data point to the developing hippocampus as a susceptible region to DLM-induced adverse effects.