Early postnatal exposure to permethrin and deltamethrin mixtures induces sex-specific hippocampal neurobehavioral and neurochemical alterations in adulthood

1. Neurotoxicology. 2026 May;114:103468. doi: 10.1016/j.neuro.2026.103468. Epub
2026 May 22.

Early postnatal exposure to permethrin and deltamethrin mixtures induces
sex-specific hippocampal neurobehavioral and neurochemical alterations in
adulthood.

Ben Slimene S(1), Boukholda K(2), Ammar R(1), Aman C(3), Allain AE(3), De
Deurwaerdère P(3), Boudawara O(4), Chagraoui A(5), Bouchard M(6), Fetoui H(7).

Author information:
(1)Laboratory of Toxicology-Microbiology and Environmental Health (17ES06),
Faculty of Sciences of Sfax, University of Sfax, BP1171, Sfax 3000, Tunisia.
(2)Laboratory of Toxicology-Microbiology and Environmental Health (17ES06),
Faculty of Sciences of Sfax, University of Sfax, BP1171, Sfax 3000, Tunisia;
Department of Neurobiology, Center for Neurotrauma, Multiomics & Biomarkers,
Morehouse School of Medicine, Atlanta, GA, USA.
(3)Institut des Neurosciences Intégratives et Cognitives d’Aquitaine, UMR 5287,
Centre National de la Recherche Scientifique, University of Bordeaux, Bordeaux,
France.
(4)Histopathology Laboratory, Department of Pathology, CHU Habib Bourguiba,
University of Sfax, Sfax, Tunisia.
(5)Department of Medical Biochemistry, Rouen University Hospital, CHU de Rouen,
France; UNIROUEN, Inserm U1239, Neuroendocrine, Endocrine and Germinal
Differentiation and Communication (NorDiC), Rouen Normandie University,
Mont-Saint-Aignan 76000, France.
(6)Department of Environmental and Occupational Health, Chair in Toxicological
Risk Assessment and Management, and Public Health Research Center (CReSP),
University of Montreal, Roger-Gaudry Building, U436, P.O. Box 6128, Main
Station, Montreal, Quebec H3C 3J7, Canada.
(7)Laboratory of Toxicology-Microbiology and Environmental Health (17ES06),
Faculty of Sciences of Sfax, University of Sfax, BP1171, Sfax 3000, Tunisia.
Electronic address: .

Pyrethroid insecticides, including deltamethrin and permethrin, are known for
their individual toxic effects; however, evidence regarding their combined
toxicity during early developmental stages remains limited. The present study
aimed to investigate the neurotoxic effects of co-exposure to deltamethrin and
permethrin in lactating rats, focusing on emotional and cognitive behaviors, as
well as cholinergic and monoaminergic neurotransmission in their progeny at
adulthood (5 months of age). Dams were orally administered deltamethrin
(1.35 mg/kg/day) and permethrin (34 mg/kg/day), either individually or in
combination, from postnatal day (PND) 7 to PND 21. Our results demonstrated that
co-exposure of lactating females to deltamethrin and permethrin induced
behavioral alterations in their offspring, including impaired locomotor
activity, anxiety-like behavior, and learning and memory deficits, with
sex-specific effects. Furthermore, these toxicants triggered oxidative stress in
the hippocampus, as indicated by elevated levels of malondialdehyde, nitric
oxide, and advanced oxidation protein products, along with impaired enzymatic
and non-enzymatic antioxidant defenses. Early postnatal exposure also caused
sex-dependent modifications in monoamine concentrations across multiple brain
regions. Mechanistically, molecular alterations of the cholinergic system were
observed in the hippocampus of both male and female rats, as evidenced by
downregulation of AChE, mAChR, and nAChR gene expression. These molecular
changes were further confirmed by histological analyses. In conclusion, our
findings demonstrate that exposure of lactating females to deltamethrin and
permethrin, individually or in combination, induces sex-dependent, deleterious,
and sometimes distinct neurodevelopmental effects in their offspring at PND 150.

Copyright © 2026 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.neuro.2026.103468
PMID: 42173172 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of Competing Interest The authors
declare that they have no known competing financial interests or personal
relationships that could have influenced the work reported in this study.

Auteurs Bordeaux Neurocampus