Expression of the cold thermoreceptor TRPM8 in rodent brain thermoregulatory circuits
Expression of the cold thermoreceptor TRPM8 in rodent brain thermoregulatory circuits
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DOI：
10.1002/cne.24694
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发表时间：
2021-01-01
影响因子：
2.5
通讯作者：
Senaris, Rosa
中科院分区：
文献类型：
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作者：
Ordas, Purificacion;Hernandez-Ortego, Pablo;Senaris, Rosa
冷和薄荷醇激活的离子通道瞬时受体电位通道亚家族M成员8（TRPM 8）是哺乳动物感觉神经末梢中环境冷的主要检测器。虽然它主要在外周感觉神经元的亚群中表达，但它也已在非神经元组织中被鉴定。在这里，我们表明，通过原位杂交（ISH）和两个不同的报告小鼠品系的转基因报告表达的分析，TRPM8也在中枢神经系统中表达。尽管TRPM8的表达水平比外周感觉神经元低得多，但我们发现TRPM8在大脑的有限区域中表达，特别是在下丘脑、隔膜、丘脑网状核、某些皮质和其他边缘结构以及脑干的一些特定核团中。有趣的是，还发现阳性纤维穿过主要的边缘束，表明TRPM8表达的中枢神经元在热调节的多个方面发挥作用，包括自主和行为热调节。大鼠脑中的额外ISH实验证明了啮齿动物物种之间该离子通道的保守表达模式。我们证实了这个通道在小鼠大脑中的功能活动，使用隔神经元的电生理膜片钳记录。这些结果为TRPM8生理学打开了一扇新的窗口，指导进一步努力了解这种分子传感器在大脑中的潜在作用。
The cold- and menthol-activated ion channel transient receptor potential channel subfamily M member 8 (TRPM8) is the principal detector of environmental cold in mammalian sensory nerve endings. Although it is mainly expressed in a subpopulation of peripheral sensory neurons, it has also been identified in non-neuronal tissues. Here, we show, by in situ hybridization (ISH) and by the analysis of transgenic reporter expression in two different reporter mouse strains, that TRPM8 is also expressed in the central nervous system. Although it is present at much lower levels than in peripheral sensory neurons, we found cells expressing TRPM8 in restricted areas of the brain, especially in the hypothalamus, septum, thalamic reticular nucleus, certain cortices and other limbic structures, as well as in some specific nuclei in the brainstem. Interestingly, positive fibers were also found traveling through the major limbic tracts, suggesting a role of TRPM8-expressing central neurons in multiple aspects of thermal regulation, including autonomic and behavioral thermoregulation. Additional ISH experiments in rat brain demonstrated a conserved pattern of expression of this ion channel between rodent species. We confirmed the functional activity of this channel in the mouse brain using electrophysiological patch-clamp recordings of septal neurons. These results open a new window in TRPM8 physiology, guiding further efforts to understand potential roles of this molecular sensor within the brain.