Romanian Society of Pharmaceutical Sciences
 

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NEURODEVELOPMENTAL DISRUPTION INDUCED BY LONG-TERM LOW-DOSE HERBICIDE EXPOSURE: BEHAVIORAL AND NEUROPATHOLOGICAL EVIDENCE FROM A RAT MODEL

ADRIANA MARIA CONSTANTINESCU 1, LILIANA CERCELARU 2, RADU MITRUT 3 , ANTONIA BLENDEA 4, PARASKEVI MARIA NECHALIOTI 5, ROBIN MESNAGE 6,7, MICHAEL N ANTONIOU 6, ARISTIDIS TSATSAKIS 8,9,10, DEMETRIOS KOURETAS 5, MICHAEL ASCHNER 11, DANIELA CALINA 12, ANCA OANA DOCEA 13*, BODGAN CATALIN 14,15

1 Doctoral School, University of Medicine and Pharmacy of Craiova, Romania
2 Department of Anatomy and Embryology, University of Medicine and Pharmacy of Craiova, Romania
3 Department of Cardiology, County Emergency Clinical Hospital of Craiova, Craiova, Romania
4 Department of Pharmaceutical Botany, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania
5 Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 41500, Larissa, Greece
6 King’s College London, Gene Expression and Therapy Group, Department of Medical and Molecular Genetics, Faculty of Life Sciences and Medicine, Guy's Hospital, London, SE1 9RT, UK
7 Buchinger Wilhelmi Clinic, Wilhelmi-Beck-Straße 27, 88662 Überlingen, Germany
8 Center of Toxicology Science & Research, Division of Morphology, Medical School, University of Crete, Voutes Campus, 71003 Heraklion, Greece
9 Faculty of Health Sciences and Human Development, Universidad ECOTEC, Samborondón 13.5 Km, Samborondón EC092302, Ecuador
10 I. M. Sechenov First Moscow State Medical University, Moscow 119435, Russia
11 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
12 Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, Romania
13 Department of Toxicology, University of Medicine and Pharmacy of Craiova, Romania
14 Experimental Research Center for Normal and Pathological Aging (ARES), University of Medicine and Pharmacy of Craiova, Craiova, Romania
15 Department of Physiology, University of Medicine and Pharmacy of Craiova, Craiova, Romania

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This study evaluated the effects of prolonged exposure to environmentally relevant levels of glyphosate, administered alone or in combination with dicamba and 2,4-dichlorophenoxyacetic acid (2,4-D), on behavioral outcomes and brain integrity in a rat model. Exposure was initiated during gestation and continued through postnatal development until early adulthood. Animals subjected to herbicide exposure exhibited alterations in locomotor activity, anxiety-related behavior, stress responses, and mo- tor coordination, with more pronounced effects observed following combined exposure. These functional changes were asso- ciated with histopathological evidence of neuronal degeneration and vascular alterations, alongside biochemical indicators of oxidative imbalance in brain tissue. Our findings indicate that chronic exposure to low-dose herbicides during critical neuro- developmental windows may induce persistent neurobehavioral and structural brain changes. The enhanced effects observed under mixture exposure conditions highlight the importance of considering combined environmental exposures in toxicological risk assessment.