Transcriptomic Profile Analysis of Brain Tissue in the Absence of Functional TRPM8 Calcium Channel

<b>Background/Objectives:</b> Transient Receptor Potential Melastatin 8 (TRPM8) is a non-selective, Ca<sup>2+</sup>-permeable cation channel involved in thermoregulation and other physiological processes, such as basal tear secretion, cell differentiation, and insulin homeost...

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Main Authors: Erick B. Saldes, Alexandra Erdmier, Jai Velpula, Timothy E. Koeltzow, Michael X. Zhu, Swapna Asuthkar
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/1/75
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author Erick B. Saldes
Alexandra Erdmier
Jai Velpula
Timothy E. Koeltzow
Michael X. Zhu
Swapna Asuthkar
author_facet Erick B. Saldes
Alexandra Erdmier
Jai Velpula
Timothy E. Koeltzow
Michael X. Zhu
Swapna Asuthkar
author_sort Erick B. Saldes
collection DOAJ
description <b>Background/Objectives:</b> Transient Receptor Potential Melastatin 8 (TRPM8) is a non-selective, Ca<sup>2+</sup>-permeable cation channel involved in thermoregulation and other physiological processes, such as basal tear secretion, cell differentiation, and insulin homeostasis. The activation and deactivation of TRPM8 occur through genetic modifications, channel interactions, and signaling cascades. Recent evidence suggests a significant role of TRPM8 in the hypothalamus and amygdala related to pain sensation and sexual behavior. Notably, TRPM8 has been implicated in neuropathic pain, migraines, and neurodegenerative diseases such as Parkinson’s disease. Our laboratory has identified testosterone as a high-affinity ligand of TRPM8. TRPM8 deficiency appears to influence behavioral traits in mice, like increased aggression and deficits in sexual satiety. Here, we aim to explore the pathways altered in brain tissues of TRPM8-deficient mice using the expression and methylation profiles of messenger RNA (mRNA) and long non-coding RNA (lncRNA). Specifically, we focused on brain regions integral to behavioral and hormonal control, including the olfactory bulb, hypothalamus, amygdala, and insula. <b>Methods:</b> RNA was isolated and purified for microarray analysis collected from male wild-type and TRPM8 knockout mice. <b>Results:</b> We identified various differentially expressed genes tied to multiple signaling pathways. Among them, the androgen–estrogen receptor (AR-ER) pathway, steroidogenesis pathway, sexual reward pathway, and cocaine reward pathway are particularly worth noting. <b>Conclusions:</b> These results should bridge the existing gaps in the knowledge regarding TRPM8 and inform potential targets for future studies to elucidate its role in the behavior changes and pathology of the diseases associated with TRPM8 activity.
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spelling doaj-art-4eea6a897af54b398ea96677ece64a122025-01-24T13:23:55ZengMDPI AGBiomedicines2227-90592024-12-011317510.3390/biomedicines13010075Transcriptomic Profile Analysis of Brain Tissue in the Absence of Functional TRPM8 Calcium ChannelErick B. Saldes0Alexandra Erdmier1Jai Velpula2Timothy E. Koeltzow3Michael X. Zhu4Swapna Asuthkar5Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine Peoria, Peoria, IL 61605, USADepartment of Cancer Biology and Pharmacology, University of Illinois College of Medicine Peoria, Peoria, IL 61605, USAPringle Robotics, Peoria, IL 61605, USADepartment of Cancer Biology and Pharmacology, University of Illinois College of Medicine Peoria, Peoria, IL 61605, USADepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USADepartment of Cancer Biology and Pharmacology, University of Illinois College of Medicine Peoria, Peoria, IL 61605, USA<b>Background/Objectives:</b> Transient Receptor Potential Melastatin 8 (TRPM8) is a non-selective, Ca<sup>2+</sup>-permeable cation channel involved in thermoregulation and other physiological processes, such as basal tear secretion, cell differentiation, and insulin homeostasis. The activation and deactivation of TRPM8 occur through genetic modifications, channel interactions, and signaling cascades. Recent evidence suggests a significant role of TRPM8 in the hypothalamus and amygdala related to pain sensation and sexual behavior. Notably, TRPM8 has been implicated in neuropathic pain, migraines, and neurodegenerative diseases such as Parkinson’s disease. Our laboratory has identified testosterone as a high-affinity ligand of TRPM8. TRPM8 deficiency appears to influence behavioral traits in mice, like increased aggression and deficits in sexual satiety. Here, we aim to explore the pathways altered in brain tissues of TRPM8-deficient mice using the expression and methylation profiles of messenger RNA (mRNA) and long non-coding RNA (lncRNA). Specifically, we focused on brain regions integral to behavioral and hormonal control, including the olfactory bulb, hypothalamus, amygdala, and insula. <b>Methods:</b> RNA was isolated and purified for microarray analysis collected from male wild-type and TRPM8 knockout mice. <b>Results:</b> We identified various differentially expressed genes tied to multiple signaling pathways. Among them, the androgen–estrogen receptor (AR-ER) pathway, steroidogenesis pathway, sexual reward pathway, and cocaine reward pathway are particularly worth noting. <b>Conclusions:</b> These results should bridge the existing gaps in the knowledge regarding TRPM8 and inform potential targets for future studies to elucidate its role in the behavior changes and pathology of the diseases associated with TRPM8 activity.https://www.mdpi.com/2227-9059/13/1/75TRPM8mRNALncRNAmethylationandrogenbrain
spellingShingle Erick B. Saldes
Alexandra Erdmier
Jai Velpula
Timothy E. Koeltzow
Michael X. Zhu
Swapna Asuthkar
Transcriptomic Profile Analysis of Brain Tissue in the Absence of Functional TRPM8 Calcium Channel
Biomedicines
TRPM8
mRNA
LncRNA
methylation
androgen
brain
title Transcriptomic Profile Analysis of Brain Tissue in the Absence of Functional TRPM8 Calcium Channel
title_full Transcriptomic Profile Analysis of Brain Tissue in the Absence of Functional TRPM8 Calcium Channel
title_fullStr Transcriptomic Profile Analysis of Brain Tissue in the Absence of Functional TRPM8 Calcium Channel
title_full_unstemmed Transcriptomic Profile Analysis of Brain Tissue in the Absence of Functional TRPM8 Calcium Channel
title_short Transcriptomic Profile Analysis of Brain Tissue in the Absence of Functional TRPM8 Calcium Channel
title_sort transcriptomic profile analysis of brain tissue in the absence of functional trpm8 calcium channel
topic TRPM8
mRNA
LncRNA
methylation
androgen
brain
url https://www.mdpi.com/2227-9059/13/1/75
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