The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia

eLife

András Matolcsy¹  Gergely Rácz¹  Michael D Culler²  Norbert Solymosi³  Szilárd Póliska⁴  Ferenc Erdélyi⁵  Gábor Szabó⁵  Blanka Tóth⁶  Csaba Vastagh⁷  Miklós Sárvári⁸  Katalin Skrapits⁸  Balázs Göcz⁸  Éva Rumpler⁸  Szabolcs Takács⁸  Viktória Váczi⁸  Imre Farkas⁸  Erik Hrabovszky⁸  Ludovica Cotellessa⁹  Vincent Prévot⁹  Cecile Allet⁹  Paolo Giacobini⁹ 

[1] 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary;Amolyt Pharma, Newton, France;Centre for Bioinformatics, University of Veterinary Medicine, Budapest, Hungary;Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;Department of Gene Technology and Developmental Biology, Institute of Experimental Medicine, Budapest, Hungary;Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Budapest, Hungary;Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Budapest, Hungary;Laboratory of Reproductive Neurobiology, Institute of Experimental Medicine, Budapest, Hungary;Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, Lille, France;

关键词: cholinergic interneurons;    GnRH;    human transcriptomics;    neuropeptides;    RNA-sequencing;    striatum;    Human;   

DOI  :  10.7554/eLife.67714

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Human reproduction is controlled by ~2000 hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Here, we report the discovery and characterization of additional ~150,000–200,000 GnRH-synthesizing cells in the human basal ganglia and basal forebrain. Nearly all extrahypothalamic GnRH neurons expressed the cholinergic marker enzyme choline acetyltransferase. Similarly, hypothalamic GnRH neurons were also cholinergic both in embryonic and adult human brains. Whole-transcriptome analysis of cholinergic interneurons and medium spiny projection neurons laser-microdissected from the human putamen showed selective expression of GNRH1 and GNRHR1 autoreceptors in the cholinergic cell population and uncovered the detailed transcriptome profile and molecular connectome of these two cell types. Higher-order non-reproductive functions regulated by GnRH under physiological conditions in the human basal ganglia and basal forebrain require clarification. The role and changes of GnRH/GnRHR1 signaling in neurodegenerative disorders affecting cholinergic neurocircuitries, including Parkinson’s and Alzheimer’s diseases, need to be explored.

【 授权许可】

CC BY