Sola Vendrell, EmmaMoyano-Cires Ivanoff, Paula VivianaFlores AGarcía Lobo, JimenaGarcía Sánchez, José ManuelFrejo Moya, María TeresaAnadón Baselga, María JoséPelayo Alarcón, AdelaFernández Fernández, María De La CabezaDel Pino JPino Sans, Javier Del2025-01-222025-01-222021Sola, E., Moyano, P., Flores, A., García, J., García, J. M., Anadon, M. J., Frejo, M. T., Pelayo, A., de la Cabeza Fernandez, M., & del Pino, J. (2022). Cadmium-induced neurotoxic effects on rat basal forebrain cholinergic system through thyroid hormones disruption. Environmental Toxicology and Pharmacology, 90. https://doi.org/10.1016/J.ETAP.2021.1037911382-668910.1016/j.etap.2021.103791https://hdl.handle.net/20.500.14352/115572Emma Sola: Methodology, Investigation, Writing – original draft, Writing – review & editing. Paula Moyano: Methodology, Investiga tion, Writing – original draft, Writing – review & editing. Andrea Flores: Methodology, Investigation, Writing – original draft, Writing – review & editing. Jimena García: Investigation, Writing – original draft, Writing – review & editing. Jose ´ Manuel García: Methodology, Investigation, Validation, Writing- Reviewing and Editing. Maria Jose Anadon: Methodology, Data curation, Writing – review & editing. María Teresa Frejo: Formal analysis, Writing – review & editing. Adela Pelayo: Resources, Formal analysis, Data curation, Supervision. Maria de la Cabeza Fernandez: Investigation, Writing – review & editing. Javier Del Pino: Conceptualization, Methodology, Project administra tion, Supervision, Writing – review & editing.Cadmium (Cd) single and repeated exposure produces cognitive dysfunctions. Basal forebrain cholinergic neu rons (BFCN) regulate cognitive functions. BFCN loss or cholinergic neurotransmission dysfunction leads to cognitive disabilities. Thyroid hormones (THs) maintain BFCN viability and functions, and Cd disrupts their levels. However, Cd-induced BFCN damages and THs disruption involvement was not studied. To research this we treated male Wistar rats intraperitoneally with Cd once (1 mg/kg) or repetitively for 28 days (0.1 mg/kg) with/without triiodothyronine (T3, 40 µg/kg/day). Cd increased thyroid-stimulating-hormone (TSH) and decreased T3 and tetraiodothyronine (T4). Cd altered cholinergic transmission and induced a more pronounced neurodegeneration on BFCN, mediated partially by THs reduction. Additionally, Cd antagonized muscarinic 1 receptor (M1R), overexpressed acetylcholinesterase S variant (AChE-S), downregulated AChE-R, M2R, M3R and M4R, and reduced AChE and choline acetyltransferase activities through THs disruption. These results may assist to discover cadmium mechanisms that induce cognitive disabilities, revealing a new possible therapeutic tool.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal article1872-7077https://doi.org/10.1016/j.etap.2021.10379134968718open access615.9CadmiumBasal forebrain cholinergic neuronsAChEChATT3M1R and M3RToxicología (Medicina)3214 Toxicología