Analysis of arsenic-modulated expression of hypothalamic estrogen receptor, thyroid receptor, and peroxisome proliferator-activated receptor gamma mRNA and simultaneous mitochondrial morphology and respiration rates in the mouse

• Published in: PloS one Vol. 19; no. 5; p. e0303528
• Main Authors: Alymbaeva, Daiana, Szabo, Csaba, Jocsak, Gergely, Bartha, Tibor, Zsarnovszky, Attila, Kovago, Csaba, Ondrasovicova, Silvia, Kiss, David Sandor
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.05.2024; Public Library of Science (PLoS)
• Subjects: Agouti-related protein; Animals; Arsenic; Arsenic - toxicity; Biology and Life Sciences; Blood-brain barrier; Brain; Brain research; Cell Respiration - drug effects; Drinking water; Energy; Estrogen; Estrogen receptors; Estrogens; Experiments; Gender differences; Gene expression; Gene Expression Regulation - drug effects; Hormones; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; Injection; Intermedin; Male; Medicine and Health Sciences; Messenger RNA; Metabolism; Mice; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Morphology; Peroxisome proliferator-activated receptors; Phenols; Physical Sciences; Physiology; Pilot projects; PPAR gamma - genetics; PPAR gamma - metabolism; Proopiomelanocortin; Receptors; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Receptors, Thyroid Hormone - genetics; Receptors, Thyroid Hormone - metabolism; Regulation; Research and Analysis Methods; Respiration; RNA, Messenger - genetics; RNA, Messenger - metabolism; Thyroid; Thyroid gland; Thyroid hormone receptors; Toxicants; Ultrastructure; Hungary
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0303528

Arsenic has been identified as an environmental toxicant acting through various mechanisms, including the disruption of endocrine pathways. The present study assessed the ability of a single intraperitoneal injection of arsenic, to modify the mRNA expression levels of estrogen- and thyroid hormone receptors (ERα,β; TRα,β) and peroxisome proliferator-activated receptor gamma (PPARγ) in hypothalamic tissue homogenates of prepubertal mice in vivo. Mitochondrial respiration (MRR) was also measured, and the corresponding mitochondrial ultrastructure was analyzed. Results show that ERα,β, and TRα expression was significantly increased by arsenic, in all concentrations examined. In contrast, TRβ and PPARγ remained unaffected after arsenic injection. Arsenic-induced dose-dependent changes in state 4 mitochondrial respiration (St4). Mitochondrial morphology was affected by arsenic in that the 5 mg dose increased the size but decreased the number of mitochondria in agouti-related protein- (AgRP), while increasing the size without affecting the number of mitochondria in pro-opiomelanocortin (POMC) neurons. Arsenic also increased the size of the mitochondrial matrix per host mitochondrion. Complex analysis of dose-dependent response patterns between receptor mRNA, mitochondrial morphology, and mitochondrial respiration in the neuroendocrine hypothalamus suggests that instant arsenic effects on receptor mRNAs may not be directly reflected in St3-4 values, however, mitochondrial dynamics is affected, which predicts more pronounced effects in hypothalamus-regulated homeostatic processes after long-term arsenic exposure.