Hindbrain Lactoprivic Regulation of Hypothalamic Third Ventricular Alpha-2 Tanycyte Metabolic Sensor Gene Expression in Hypoglycemic Male Versus Female Rats

IF 3.8 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemical Research Pub Date : 2025-09-04 DOI:10.1007/s11064-025-04533-5

Rajesh K. Yadav, Subash Sapkota, Karen P. Briski

{"title":"Hindbrain Lactoprivic Regulation of Hypothalamic Third Ventricular Alpha-2 Tanycyte Metabolic Sensor Gene Expression in Hypoglycemic Male Versus Female Rats","authors":"Rajesh K. Yadav, Subash Sapkota, Karen P. Briski","doi":"10.1007/s11064-025-04533-5","DOIUrl":null,"url":null,"abstract":"<div><p>Alpha-2 (α2-) tanycytes line the ventral wall of the third ventricle where they ostensibly engage in metabolic screening. The oxidizable glycolytic end-product L-lactate is a gauge of hindbrain energy stability that is imparted to forebrain glucose-regulatory loci by norepinephrine signaling. Current research used a validated whole-animal model for insulin-induced hypoglycemia (IIH) to address the premise that hindbrain lactate status imposes sex-specific control of eu- and/or hypoglycemic patterns of α2-tanycyte chemosensor gene transcription in vivo. Vimentin-immunopositive α2-tanycytes were laser-catapult-microdissected from male and female brain sections after subcutaneous insulin injection and caudal fourth ventricular (CV4) L-lactate- or vehicle infusion for single-cell multiplex qPCR analysis of glucose and energy sensor gene expression. Hindbrain lactate infusion reversed IIH repression of α2-tanycyte glucose transporter-2 mRNA in females and amplified (males) or reversed (females) up-regulated glucokinase gene transcription. Lactate increased α2-tanycyte ATP-sensitive potassium channel Kir6.2 mRNA levels in hypoglycemic rats of each sex, reversing transcriptional inhibition in males or amplifying up-regulated expression in females. In both sexes, IIH-associated down-regulation of energy sensor 5’-AMP-activated protein kinase catalytic subunit isoforms alpha-1 and − 2 gene profiles was correspondingly unaffected or reversed by lactate. Hypoglycemia increased or decreased α2-tanycyte alpha<sub>1a</sub> and beta<sub>1</sub> receptor mRNA content, respectively; lactate caused opposite, sex-specific adjustments in transcriptional reactivity of the former gene yet did not affect the latter profile in either sex. Results show that hypothalamic α2-tanycytes are direct target for norepinephrine stimulation and document sex-dimorphic hindbrain lactoprivic regulation of chemosensor gene transcriptional responses to in vivo hypoglycemia.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemical Research","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s11064-025-04533-5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Alpha-2 (α2-) tanycytes line the ventral wall of the third ventricle where they ostensibly engage in metabolic screening. The oxidizable glycolytic end-product L-lactate is a gauge of hindbrain energy stability that is imparted to forebrain glucose-regulatory loci by norepinephrine signaling. Current research used a validated whole-animal model for insulin-induced hypoglycemia (IIH) to address the premise that hindbrain lactate status imposes sex-specific control of eu- and/or hypoglycemic patterns of α2-tanycyte chemosensor gene transcription in vivo. Vimentin-immunopositive α2-tanycytes were laser-catapult-microdissected from male and female brain sections after subcutaneous insulin injection and caudal fourth ventricular (CV4) L-lactate- or vehicle infusion for single-cell multiplex qPCR analysis of glucose and energy sensor gene expression. Hindbrain lactate infusion reversed IIH repression of α2-tanycyte glucose transporter-2 mRNA in females and amplified (males) or reversed (females) up-regulated glucokinase gene transcription. Lactate increased α2-tanycyte ATP-sensitive potassium channel Kir6.2 mRNA levels in hypoglycemic rats of each sex, reversing transcriptional inhibition in males or amplifying up-regulated expression in females. In both sexes, IIH-associated down-regulation of energy sensor 5’-AMP-activated protein kinase catalytic subunit isoforms alpha-1 and − 2 gene profiles was correspondingly unaffected or reversed by lactate. Hypoglycemia increased or decreased α2-tanycyte alpha_1a and beta₁ receptor mRNA content, respectively; lactate caused opposite, sex-specific adjustments in transcriptional reactivity of the former gene yet did not affect the latter profile in either sex. Results show that hypothalamic α2-tanycytes are direct target for norepinephrine stimulation and document sex-dimorphic hindbrain lactoprivic regulation of chemosensor gene transcriptional responses to in vivo hypoglycemia.

查看原文本刊更多论文

低血糖雌雄大鼠下丘脑第三脑室α -2伸长细胞代谢传感器基因表达的后脑乳腔调节

α -2 （α2-）伸长细胞排列在第三脑室的腹壁上，在那里它们表面上参与代谢筛选。可氧化的糖酵解终产物l -乳酸是后脑能量稳定性的一个指标，它通过去甲肾上腺素信号传递给前脑葡萄糖调节位点。目前的研究使用了一个经过验证的胰岛素诱导的低血糖（IIH）全动物模型，以解决后脑乳酸状态对α2-鞣质细胞化学传感器基因转录的eu-和/或低血糖模式施加性别特异性控制的前提。在皮下注射胰岛素和尾侧第四脑室（CV4） l -乳酸或车辆输注后，用激光弹射器显微解剖vimentin免疫阳性α2-tanycytes，用于单细胞多重qPCR分析葡萄糖和能量传感器基因表达。后脑乳酸输注逆转了IIH对女性α -2 -鞣质细胞葡萄糖转运体-2 mRNA的抑制，并扩增（雄性）或逆转（雌性）上调葡萄糖激酶基因转录。乳酸升高了各性别低血糖大鼠α2-坦尼细胞atp敏感钾通道Kir6.2 mRNA水平，在雄性中逆转了转录抑制，在雌性中放大了上调表达。在两性中，iiih相关的能量传感器5 ' - amp激活的蛋白激酶催化亚基亚型α -1和- 2基因谱的下调相应地不受乳酸的影响或逆转。低血糖分别升高或降低α2-鞣皮细胞α 1a和β 1受体mRNA含量；乳酸在前一基因的转录反应性中引起相反的、性别特异性的调整，但对后一基因在两性中都没有影响。结果表明下丘脑α2-tanycytes是去甲肾上腺素刺激的直接靶点，并记录了性别二态的后脑乳腔调节对体内低血糖的化学传感器基因转录反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Neurochemical Research 医学-神经科学

CiteScore

7.70

自引率

2.30%

发文量

320

审稿时长

6 months

期刊介绍： Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.