Cadmium-induced neurotoxic effects on rat basal forebrain cholinergic system through thyroid hormones disruption

Autor: Emma Sola, Paula Moyano, Andrea Flores, Jimena García, José Manuel García, María José Anadon, María Teresa Frejo, Adela Pelayo, Maria de la Cabeza Fernandez, Javier del Pino
Rok vydání: 2021
Předmět:
Zdroj: E-Prints Complutense. Archivo Institucional de la UCM
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ISSN: 1872-7077
Popis: 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.
Databáze: OpenAIRE
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