Sola Vendrell, EmmaMoyano-Cires Ivanoff, Paula VivianaFlores AGarcía Sánchez, José ManuelGarcía Lobo, JimenaAnadón Baselga, María JoséFrejo Moya, María TeresaPelayo Alarcón, AdelaFernández Fernández, María De La CabezaPino Sans, Javier Del2025-01-212025-01-212023-02-28Sola, E., Moyano, P., Flores, A., García, J. M., García, J., Anadon, M. J., Frejo, M. T., Pelayo, A., de la Cabeza Fernandez, M., & Del Pino, J. (2023). Cadmium-promoted thyroid hormones disruption mediates ROS, inflammation, Aβ and Tau proteins production, gliosis, spongiosis and neurodegeneration in rat basal forebrain. Chemico-biological interactions, 375, 110428. https://doi.org/10.1016/j.cbi.2023.1104280009-279710.1016/j.cbi.2023.110428https://hdl.handle.net/20.500.14352/115389Author contribution statement: Emma Sola: Methodology, Investigation, Writing- Original draft preparation, Writing- Reviewing and Editing. Paula Moyano: Methodology, Investigation, Writing- Original draft preparation, WritingReviewing and Editing. Andrea Flores: Methodology, Investigation, Writing- Original draft preparation, Writing- Reviewing and Editing. Jimena García: Investigation, Writing- Original draft preparation, Writing- Reviewing and Editing. Jos´e Manuel García: Methodology, Investigation, Validation, Writing- Reviewing and Editing. Maria Jose Anadon: Methodology, Data curation, Writing- Reviewing and Editing. María Teresa Frejo: Formal analysis, Writing- Reviewing and Editing. Adela Pelayo: Resources, Formal analysis, Data curation, Supervision. Maria de la Cabeza Fernandez: Investigation, Writing- Reviewing and Editing. Javier Del Pino: Conceptualization, Methodology, Project administration, Supervision, Writing- Reviewing and EditingCadmium (Cd) produces cognition decline following single and repeated treatment, although the complete mechanisms are still unrevealed. Basal forebrain (BF) cholinergic neurons innervate the cortex and hippocampus, regulating cognition. Cd single and repeated exposure induced BF cholinergic neuronal loss, partly through thyroid hormones (THs) disruption, which may cause the cognition decline observed following Cd exposure. However, the mechanisms through which THs disruption mediate this effect remain unknown. To research the possible mechanisms through which Cd-induced THs deficiency may mediate BF neurodegeneration, Wistar male rats were treated with Cd for 1- (1 mg/kg) or 28-days (0.1 mg/kg) with or without triiodothyronine (T3, 40 μg/kg/day). Cd exposure promoted neurodegeneration, spongiosis, gliosis and several mechanisms related to these alterations (increased H202, malondialdehyde, TNF-α, IL-1β, IL-6, BACE1, Aβ and phosphorylated-Tau levels, and decreased phosphorylated-AKT and phosphorylated-GSK-3β levels). T3 supplementation partially reversed the effects observed. Our results show that Cd induces several mechanisms that may be responsible for the neurodegeneration, spongiosis and gliosis observed in the rats’ BF, which are partially mediated by a reduction in THs levels. These data may help to explain the mechanisms through which Cd induces BF neurodegeneration, possibly leading to the cognitive decline observed, providing new therapeutic tools to prevent and treat these damages.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal article1872-7786https://doi.org/10.1016/j.cbi.2023.11042836868496open access615.9CadmiumBasal forebrain cholinergic neuronsInflammatory cytokinesAβ and Tau proteinsT3Oxidative stressToxicología (Medicina)3214 Toxicología