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

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 ex...

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Main Authors: Katalin Skrapits, Miklós Sárvári, Imre Farkas, Balázs Göcz, Szabolcs Takács, Éva Rumpler, Viktória Váczi, Csaba Vastagh, Gergely Rácz, András Matolcsy, Norbert Solymosi, Szilárd Póliska, Blanka Tóth, Ferenc Erdélyi, Gábor Szabó, Michael D Culler, Cecile Allet, Ludovica Cotellessa, Vincent Prévot, Paolo Giacobini, Erik Hrabovszky
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-06-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/67714
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author Katalin Skrapits
Miklós Sárvári
Imre Farkas
Balázs Göcz
Szabolcs Takács
Éva Rumpler
Viktória Váczi
Csaba Vastagh
Gergely Rácz
András Matolcsy
Norbert Solymosi
Szilárd Póliska
Blanka Tóth
Ferenc Erdélyi
Gábor Szabó
Michael D Culler
Cecile Allet
Ludovica Cotellessa
Vincent Prévot
Paolo Giacobini
Erik Hrabovszky
author_facet Katalin Skrapits
Miklós Sárvári
Imre Farkas
Balázs Göcz
Szabolcs Takács
Éva Rumpler
Viktória Váczi
Csaba Vastagh
Gergely Rácz
András Matolcsy
Norbert Solymosi
Szilárd Póliska
Blanka Tóth
Ferenc Erdélyi
Gábor Szabó
Michael D Culler
Cecile Allet
Ludovica Cotellessa
Vincent Prévot
Paolo Giacobini
Erik Hrabovszky
author_sort Katalin Skrapits
collection DOAJ
description 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.
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spelling doaj.art-a6f90203e0064aa79d6e78b486c43b012022-12-22T03:33:56ZengeLife Sciences Publications LtdeLife2050-084X2021-06-011010.7554/eLife.67714The cryptic gonadotropin-releasing hormone neuronal system of human basal gangliaKatalin Skrapits0Miklós Sárvári1Imre Farkas2https://orcid.org/0000-0002-0159-4408Balázs Göcz3Szabolcs Takács4Éva Rumpler5Viktória Váczi6Csaba Vastagh7Gergely Rácz8András Matolcsy9Norbert Solymosi10https://orcid.org/0000-0003-1783-2041Szilárd Póliska11Blanka Tóth12Ferenc Erdélyi13Gábor Szabó14Michael D Culler15Cecile Allet16Ludovica Cotellessa17Vincent Prévot18Paolo Giacobini19https://orcid.org/0000-0002-3075-1441Erik Hrabovszky20https://orcid.org/0000-0001-6927-0015Laboratory of Reproductive Neurobiology, Institute of Experimental Medicine, Budapest, HungaryLaboratory of Reproductive Neurobiology, Institute of Experimental Medicine, Budapest, HungaryLaboratory of Reproductive Neurobiology, Institute of Experimental Medicine, Budapest, HungaryLaboratory of Reproductive Neurobiology, Institute of Experimental Medicine, Budapest, HungaryLaboratory of Reproductive Neurobiology, Institute of Experimental Medicine, Budapest, HungaryLaboratory of Reproductive Neurobiology, Institute of Experimental Medicine, Budapest, HungaryLaboratory of Reproductive Neurobiology, Institute of Experimental Medicine, Budapest, HungaryLaboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Budapest, Hungary1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, HungaryCentre for Bioinformatics, University of Veterinary Medicine, Budapest, HungaryDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, HungaryDepartment of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Budapest, HungaryDepartment of Gene Technology and Developmental Biology, Institute of Experimental Medicine, Budapest, HungaryDepartment of Gene Technology and Developmental Biology, Institute of Experimental Medicine, Budapest, HungaryAmolyt Pharma, Newton, FranceUniv. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, Lille, FranceUniv. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, Lille, FranceUniv. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, Lille, FranceUniv. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, Lille, FranceLaboratory of Reproductive Neurobiology, Institute of Experimental Medicine, Budapest, HungaryHuman 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.https://elifesciences.org/articles/67714cholinergic interneuronsGnRHhuman transcriptomicsneuropeptidesRNA-sequencingstriatum
spellingShingle Katalin Skrapits
Miklós Sárvári
Imre Farkas
Balázs Göcz
Szabolcs Takács
Éva Rumpler
Viktória Váczi
Csaba Vastagh
Gergely Rácz
András Matolcsy
Norbert Solymosi
Szilárd Póliska
Blanka Tóth
Ferenc Erdélyi
Gábor Szabó
Michael D Culler
Cecile Allet
Ludovica Cotellessa
Vincent Prévot
Paolo Giacobini
Erik Hrabovszky
The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia
eLife
cholinergic interneurons
GnRH
human transcriptomics
neuropeptides
RNA-sequencing
striatum
title The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia
title_full The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia
title_fullStr The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia
title_full_unstemmed The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia
title_short The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia
title_sort cryptic gonadotropin releasing hormone neuronal system of human basal ganglia
topic cholinergic interneurons
GnRH
human transcriptomics
neuropeptides
RNA-sequencing
striatum
url https://elifesciences.org/articles/67714
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