新生小鼠大脑中生长激素受体阳性神经元的分布和功能

doi:10.16098/j.issn.0529-1356.2024.04.007

解剖学报 ›› 2024, Vol. 55 ›› Issue (4): 422-429.doi: 10.16098/j.issn.0529-1356.2024.04.007

新生小鼠大脑中生长激素受体阳性神经元的分布和功能

夏宇任淑裕李涛梅峰^*

陆军军医大学基础医学院组织胚胎学教研室，重庆 400038

收稿日期:2024-01-31 修回日期:2024-04-01 出版日期:2024-08-06 发布日期:2024-08-06
通讯作者: 梅峰 E-mail:meifeng.mail@163.com
基金资助:
科技部科技创新2030-“脑科学与类脑研究”重大项目：脑智异常的脑白质发育机制-分题“脑白质发育障碍的髓鞘异质性特征及功能”

Function and distribution of growth hormone receptor positive neurons in neonatal mouse brain

XIA Yu REN Shu-yu LI Tao MEI Feng^*

Department of Histology and Embryology, School of Basic Medical Sciences, Army Medical University, Chongqing 400038, China)

Received:2024-01-31 Revised:2024-04-01 Online:2024-08-06 Published:2024-08-06
Contact: MEI Feng E-mail:meifeng.mail@163.com

摘要/Abstract

摘要： 目的探讨生长激素受体(GHR)阳性神经元在新生小鼠大脑中的分布及功能。方法选取6只GHR-CreERT; mTOMATO/mGFP荧光报告基因小鼠，均在出生后第3天使用他莫昔芬诱导，在第10天和第17天分别取材3只，观察不同发育阶段大脑中GHR阳性神经细胞的分布。构建GHR floxed小鼠，通过与神经元特异性Thy1-CreERT; YFP小鼠杂交，诱导性敲除神经元中GHR。对照小鼠（GHR fl/fl 4只）和条件敲除小鼠（Thy1; GHR fl/fl 4只），在出生后第3天诱导，于第10天取材，用于观察神经元GHR信号对大脑发育的影响。结果 GHR荧光报告基因小鼠显示GHR阳性细胞在新生小鼠大脑中广泛表达，GHR阳性神经元集中在下丘脑室旁核(PVN)；特异性敲除新生小鼠大脑神经元中的GHR，神经元以及各类胶质细胞的单位面积数量未见明显差异。结论 GHR阳性神经元主要集中在下丘脑PVN，敲除发育大脑神经元的GHR不能明显改变各种神经元和神经胶质等细胞的形态和密度。

关键词: 生长激素, 生长激素受体, 发育, 神经元, 髓鞘, 免疫荧光, 小鼠

Abstract:

Objective To study the distribution and effect of growth hormone receptor (GHR) positive neurons in neonatal mouse brain Methods Six GHR-CreERT;mTOMATO/mGFP fluorescent reporter gene mice were selected. All of them were induced with tamoxifen on the 3rd day after birth. On the 10th and 17th days, 3 mice were sampled respectively at each time point. The distribution of GHR-positive neurons in the developing brain was observed at different stages. GHR floxed mice were generated. By crossing them with neuron-specific Thy1-CreERT;YFP mice, GHR was induced to be knocked out in neurons. Control mice (GHR fl/fl, 4 mice) and conditional knockout mice (Thy1-CreERT;YFP;GHR fl/fl, 4 mice) were induced on the 3rd day after birth. Samples were collected on the 10th day for observing the effect of neuronal GHR signaling on brain development. Results The GHR fluorescent reporter gene mice showed that GHR-positive cells are widely expressed in the developing mouse brain. GHR-positive neurons are concentrated in the paraventricular hypothalamic nucleus (PVN). After specifically knocking out GHR in neurons of the developing mouse brain, no significant differences were observed in the areal densities of neurons and various types of glial cells. Conclusion GHR-positive neurons are mainly concentrated in the PVN. Knocking out GHR in neurons of the developing brain cannot significantly change the morphology and density of various neural cell types.

Key words: Growth hormone, Growth hormone receptor, Development, Neuron, Myelin sheath, Immunofluorescence, Mouse

中图分类号:

R329.4

夏宇任淑裕李涛梅峰. 新生小鼠大脑中生长激素受体阳性神经元的分布和功能[J]. 解剖学报, 2024, 55(4): 422-429.

XIA Yu REN Shu-yu LI Tao MEI Feng. Function and distribution of growth hormone receptor positive neurons in neonatal mouse brain[J]. Acta Anatomica Sinica, 2024, 55(4): 422-429.

参考文献

［1］Ranke MB, Wit JM. Growth hormone-past, present and future ［J］. Nat Rev Endocrinol, 2018, 14(5): 285-300.

［2］M∅ller N, J∅rgensen JOL. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects ［J］. Endocr Rev, 2009, 30(2): 152-177.

［3］Ran L, Wang X, Mi A, et al. Loss of adipose growth hormone receptor in mice enhances local fatty acid trapping and impairs brown adipose tissue thermogenesis ［J］. iScience, 2019, 16: 106-121.

［4］Dixit M, Poudel SB, Yakar S. Effects of GH/IGF axis on bone and cartilage ［J］. Mol Cell Endocrinol, 2021, 519: 111052.

［5］Postel-Vinay MC, Finidori J. Growth hormone receptor: structure and signal transduction ［J］. Eur J Endocrinol, 1995, 133(6): 654-659.

［6］Vázquez-Borrego MC, Del Río-Moreno M, Pyatkov M, et al. Direct and systemic actions of growth hormone receptor (GHR)-signaling on hepatic glycolysis, de novo lipogenesis and insulin sensitivity, associated with steatosis ［J］. Metabolism, 2023, 144: 155589.

［7］Bianchi VE, Locatelli V, Rizzi L. Neurotrophic and neuroregenerative effects of GH/IGF1 ［J］. Int J Mol Sci, 2017, 18(11):2441.

［8］Poljakovic Z, Zurak N, Brinar V, et al. Growth hormone and insulin growth factor-I levels in plasma and cerebrospinal fluid of patients with multiple sclerosis ［J］. Clin Neurol Neurosurg, 2006, 108(3): 255-258.

［9］Zeng WQ, Yang Ch, Zhou X, et al. Insulin-like growth factor 1 playing a pivotal role on recovery of transient forebrain ischemia damage in neonatal rats ［J］. Acta Anatomica Sinica, 2012, 43(2): 145-149. (in Chinese)

曾文钦, 杨春, 周辛, 等. 胰岛素样生长因子1在新生大鼠短暂脑缺血损伤修复中的关键作用［J］. 解剖学报, 2012, 43(2): 145-149.

［10］van Nieuwpoort IC, Drent ML. Cognition in the adult with childhood-onset GH deficiency ［J］. Eur J Endocrinol, 2008, 159 （Suppl 1）: S53-S57.

［11］Aleman A, Verhaar HJ, De Haan EH, et al. Insulin-like growth factor-I and cognitive function in healthy older men ［J］. J Clin Endocrinol Metab, 1999, 84(2): 471-475.

［12］Wasinski F, Klein MO, Bittencourt JC, et al. Distribution of growth hormone-responsive cells in the brain of rats and mice ［J］. Brain Res, 2021, 1751: 147189.

［13］Furigo IC, Metzger M, Teixeira PDS, et al. Distribution of growth hormone-responsive cells in the mouse brain ［J］. Brain Struct Funct, 2017, 222(1): 341-363.

［14］Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering ［J］. Cell, 2014, 157(6): 1262-1278

［15］Muzumdar MD, Tasic B, Miyamichi K, et al. A global double-fluorescent Cre reporter mouse ［J］. Genesis, 2007, 45(9): 593-605.

［16］Shaner NC, Campbell RE, Steinbach PA, et al. Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein ［J］. Nat Biotechnol, 2004, 22(12): 1567-1572.

［17］Ilkbahar YN, Wu K, Thordarson G, et al. Expression and distribution of messenger ribonucleic acids for growth hormone (GH) receptor and GH-binding protein in mice during pregnancy ［J］. Endocrinology, 1995, 136(2): 386-392.

［18］Wei XT, Li LY, Zhang YT, et al. Electroacupuncture preconditioning alleviates myocardial ischemia-reperfusion injury through the hypothalamic paraventricular nucleus-interposed nucleus nerve pathway ［J］. J Tradit Chin Med, 2022, 42(3): 379-388.

［19］Young P, Qiu L, Wang D, et al. Single-neuron labeling with inducible Cre-mediated knockout in transgenic mice ［J］. Nat Neurosci, 2008, 11(6): 721-728.

［20］Wang F, Ren SY, Chen JF, et al. Myelin degeneration and diminished myelin renewal contribute to age-related deficits in memory ［J］. Nat Neurosci, 2020, 23(4): 481-486.

［21］Quaresma PGF, Dos Santos WO, Wasinski F, et al. Neurochemical phenotype of growth hormone-responsive cells in the mouse paraventricular nucleus of the hypothalamus ［J］. J Comp Neurol, 2021, 529(6): 1228-1239.

［22］Steyn FJ, Huang L, Ngo ST, et al. Development of a method for the determination of pulsatile growth hormone secretion in mice ［J］. Endocrinology, 2011, 152(8): 3165-3171.

［23］Zhang H, Han M, Zhang X, et al. The effect and mechanism of growth hormone replacement on cognitive function in rats with traumatic brain injury ［J］. PLoS One, 2014, 9(9): e108518.

[1]	杨婷廖奎黄彩虹魏晗王程杜坤航汪子铃王璐王亚平. 当归多糖促进骨髓移植重建受体小鼠造血功能[J]. 解剖学报, 2024, 55(5): 556-564.
[2]	杨云孙攀文许亚平郭志坤. 小鼠冠状动脉粥样硬化区域炎性因子对干细胞迁移的调控作用[J]. 解剖学报, 2024, 55(5): 565-572.
[3]	李月魏思萌武欣刘逍李琦陈畅. 二肽基肽酶-4抑制剂阿拉格列汀抑制结直肠癌肺转移瘤的形成及其机制#br# #br# [J]. 解剖学报, 2024, 55(5): 582-588.
[4]	陈伟陈嘉勤王一蓉. 跑台运动联合黑枸多糖改善模型小鼠的抑郁症样行为[J]. 解剖学报, 2024, 55(5): 524-532.
[5]	牟连伟韩鹏杨运杰 . 运动干预调控海马神经元自噬改善阿尔茨海默病模型小鼠学习记忆障碍[J]. 解剖学报, 2024, 55(5): 533-540.
[6]	姜新泽刘强孙旭侯姜姗马瑞程梅吴玉龙 . 微塑料暴露对小鼠学习记忆的影响及其作用机制[J]. 解剖学报, 2024, 55(5): 541-546.
[7]	王莉娟高策赵志弘海振李文惠韩秋琴. 电针调节皮层NF-κB/ NOD样受体蛋白3信号通路抑制脂多糖诱导的慢性神经炎症[J]. 解剖学报, 2024, 55(5): 547-555.
[8]	陈钧钧周立苏田王现伟张海龙王志勇. 多巴胺受体在小肠的分布与定位[J]. 解剖学报, 2024, 55(5): 612-618.
[9]	朱柯桦吴凤玲孙寒雪洪洁陈思海史娟李云庆. 调控内侧前额叶皮质向丘脑室旁核投射通路对小鼠痛信息传递的影响[J]. 解剖学报, 2024, 55(4): 430-436.
[10]	巩涛蔡志平史娟李云庆. 小鼠中缝背核向屏状核投射神经通路的形态学特征[J]. 解剖学报, 2024, 55(4): 414-421.
[11]	李海艳李忠达何立娟. 星形胶质细胞敲除铜蓝蛋白对小鼠脑铁代谢的影响[J]. 解剖学报, 2024, 55(4): 475-481.
[12]	刘晓璇张晗思韩晓静尚晓迪康静林俊堂闫欣乔梁. 瘦素对肥胖小鼠下丘脑神经元活性及脂肪组织代谢的影响[J]. 解剖学报, 2024, 55(4): 452-459.
[13]	陈婧菲肖岚. 髓鞘动态变化及其在阿尔茨海默病认知功能障碍中的作用[J]. 解剖学报, 2024, 55(4): 379-385.
[14]	宫川惠邱家怡印可馨张继茹何铖袁野吕广明. 基于灌注系统对CUBIC组织透明化技术的优化[J]. 解剖学报, 2024, 55(3): 363-370.
[15]	曹聪黄沁雯王红许泽婷张婵单亦文范肖肖廖敏 . 运动及复杂环境抑制细菌脂多糖诱导的中脑黑质多巴胺能神经元损伤[J]. 解剖学报, 2024, 55(3): 253-259.

新生小鼠大脑中生长激素受体阳性神经元的分布和功能

Function and distribution of growth hormone receptor positive neurons in neonatal mouse brain

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价