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

XIA Yu; REN Shu-Yu; LI Tao; MEI Feng

doi:10.16098/j.issn.0529-1356.2024.04.007

PDF(21332 KB)

Acta Anatomica Sinica ›› 2024, Vol. 55 ›› Issue (4) : 422-429. DOI: 10.16098/j.issn.0529-1356.2024.04.007

Research Articles

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

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

Author information +

History +

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

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

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 https://doi.org/10.16098/j.issn.0529-1356.2024.04.007

References

［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.