Evidence map›Paper›PMID 40906727›Full record

ArticlePloS one2025

GDNF receptor GFRα1 is necessary for the maintenance of dopaminergic neurons in the adult substantia nigra.

Alvaro Carrier-Ruiz, Annika Andersson, Diana Fernández-Suárez, Carlos F Ibáñez

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Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Alvaro Carrier-RuizDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.ORCID https://orcid.org/0000-0002-0889-709X
Annika AnderssonDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Diana Fernández-SuárezDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Carlos F IbáñezDepartment of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

GFRα1 and Ret are the two necessary components of the receptor for GDNF, a neurotrophic factor discovered in the early 1990's for its ability to support the survival of midbrain dopaminergic neurons, including those in the substantia nigra (SN) that project to the dorsal striatum (dSTR) and degenerate in Parkinson's Disease. Several GDNF clinical trials have been conducted to date with mixed results. Despite the physiological and clinical importance of this signaling system, whether any of its components are required for the maintenance of adult SN neurons has not yet been elucidated. In this study, we first analyzed postnatal expression patterns of Gfrα1 and Ret in the SN and established that mRNA levels peak at mouse postnatal day 15 (P15), stabilizing after P30. Using Tamoxifen-induced deletion of Gfrα1 at 3 months of age, we found that GFRα1 is required for the maintenance of a subset of adult SN dopaminergic neurons. FluoroGold tracing of SN axons from the dSTR in mutant mice revealed that ablation of GFRα1 preferentially affects the subset of GFRα1-expressing neurons that project to the STR. In addition to the well-known neuroprotective functions of GDNF/GFRα1/RET signaling, our results establish a physiological requirement of the GFRα1 component of this neurotrophic system for the continuous maintenance of SN dopaminergic neurons in the adult brain.

Indexed as

Dopaminergic NeuronsGlial Cell Line-Derived Neurotrophic Factor ReceptorsSubstantia NigraAnimalsGlial Cell Line-Derived Neurotrophic FactorMiceProto-Oncogene Proteins c-retGfra1 protein, mouseGlial Cell Line-Derived Neurotrophic FactorGlial Cell Line-Derived Neurotrophic Factor ReceptorsProto-Oncogene Proteins c-retRet protein, mouse

Identifiers

PMID40906727
PMCPMC12410770

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.