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Effect of estradiol on thermoregulatory responses in ovariectomized rats administered ostruthin, a TWIK-related potassium channel agonist

ABSTRACT: This study investigated the effects of estradiol (E2) on ostruthin-induced thermoregulatory responses in ovariectomized rats, a menopausal model. Ostruthin, a component extracted from Paramignya trimera, is an agonist of cold receptors, specifically the TWIK-related potassium channels 1 (TREK1) and 2 (TREK2). Wistar rats were ovariectomized and implanted with a silastic tube with or without E2 (E2(+) and E2(−) groups). Ostruthin or vehicle was injected intraperitoneally. Body temperature (Tb), locomotor activity, tail skin temperature (Ttail), oxygen consumption, and tail-hiding behavior were measured continuously. Plasma concentrations of catecholamines, triiodothyronine, and thyroxine were measured. mRNA expression levels of TWIK-related potassium channels, transient receptor potential cation channels, E2 receptors, and selected four genes in dorsal root ganglia were assessed. For the electrophysiological study, ventral root reflex responses induced by dorsal root stimulation were measured in in vitro preparations of neonatal rat spinal cord applied 500 μM ostruthin. Ostruthin increased Tb in the E2(+) group. In ostruthin-treated groups, Tb in the E2(+) group was greater than that in the E2(−) group. Ostruthin decreased Ttail. There was a tendency for E2 to decrease Ttail. E2 increased plasma triiodothyronine. E2 increased TREK1, nerve growth factor-inducible, and nitric oxide synthase 1 mRNA level. No significant differences in other measurements were observed among the groups. The excitation of sensory nerves by ostruthin and the increase of TREK1 by E2 may facilitate cold sensitivity. Ostruthin and E2 suppressed heat dissipation by tail skin vasomotor control. E2 may increase Tb in a menopausal model, potentially through modulation of TREK1.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE278704 | GEO | 2025/09/27

REPOSITORIES: GEO

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Project description:Tail amputation by tail docking or as an extreme consequence of tail biting in commercial pig production has serious implications for animal welfare. Tail amputation causes peripheral nerve injury that might be associated with chronic lasting pain. The aim of this study was to investigate the short- and long-term effects of tail amputation in pigs on caudal DRG gene expression at different stages of development, particularly in relation to genes associated with nociception and pain. Microarray analysis was used to analyse whole DRG transcriptomes from tail amputated and sham-treated pigs 1, 8 and 16 weeks following tail treatment at either 3 or 63 days of age (8 pigs/treatment/age/time after treatment; n=96). Tail amputation induced marked changes in gene expression (up and down) compared to sham-treated intact controls for all treatment ages and time points after tail treatment. Sustained changes in gene expression in tail amputated pigs were still evident approximately 4 months after tail injury. Gene correlation network analysis revealed two gene coexpression clusters associated with amputation. Gene ontology (GO) enrichment analysis found the genes in Cluster A (124 genes) and Cluster B (61 genes) to be associated with both ‘inflammatory pain’ and ‘neuropathic pain ’. Key families of ion channels and receptors were significantly down-regulated compared to shams in Cluster A, in particular voltage-gated potassium channels and GABA receptors which are both linked to increased peripheral nerve excitability after axotomy. Up-regulated functional gene families in Cluster B were linked to transcription regulation, inflammation, tissue remodelling and regulatory neuropeptide activity. DRG gene expression profiles appear to reflect sustained tissue inflammation and repair (ca. 4 months) and pain signal modulation consistent with adaptive, compensatory responses linked to injury induced increases in peripheral somatosensory neuronal excitability in the tail stump. Tail amputation causes acute and sustained changes in peripheral somatosensory nerve function involving key mediators of inflammatory and neuropathic pain which have implications for long-term tail stump pain. The findings of this study may have ramifications for the effects of tail amputation in other species. We used microarray to investigate the effects of tail amputation on gene expression in the dorsal root ganglia of caudal nerves in pigs at 2 treatment ages and 3 time points after tail treatment

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Effect of estradiol on thermoregulatory responses in ovariectomized rats administered ostruthin, a TWIK-related potassium channel agonist

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