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

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Sola Vendrell, Emma and Moyano-Cires Ivanoff, Paula Viviana and Flores, Andrea and Garcia Lobo, Jimena and García Sánchez, José Manuel and Anadón Baselga, María José and Frejo Moya, María Teresa and Pelayo Alarcon, Adela and Fernández Fernández, María de la Cabeza and Pino Sans, Javier del (2021) Cadmium-induced neurotoxic effects on rat basal forebrain cholinergic system through thyroid hormones disruption. Environmental Toxicology and Pharmacology, 90 . p. 103791. ISSN 1382-6689

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Official URL: 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.


Item Type:Article
Additional Information:

CRUE-CSIC (Acuerdos Transformativos 2021)

Uncontrolled Keywords:Cadmium, Basal forebrain cholinergic neurons, AChE, ChAT, T3, M1R and M3R
Subjects:Medical sciences > Veterinary > Veterinary pharmacology
ID Code:69754
Deposited On:24 Jan 2022 15:04
Last Modified:18 Oct 2022 07:48

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