Cadmium-induced neurotoxic effects on rat basal forebrain cholinergic system through thyroid hormones disruption
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2021
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Elsevier
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Sola Vendrell, E., Moyano-Cires Ivanoff, P. V., Flores, A. et al. «Cadmium-Induced Neurotoxic Effects on Rat Basal Forebrain Cholinergic System through Thyroid Hormones Disruption». Environmental Toxicology and Pharmacology, vol. 90, febrero de 2022, p. 103791. DOI.org (Crossref), https://doi.org/10.1016/j.etap.2021.103791.
Abstract
Cadmium (Cd) single and repeated exposure produces cognitive dysfunctions. Basal forebrain cholinergic neurons (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.
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