ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Nigrostriatal rAAV-mediated GDNF overexpression induces robust weight loss in a rat model of age-related obesity.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 101 citations in OpenAlex.
- Safety/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients.Neurology · 2013Trial
- Weight changes in subthalamic nucleus vs globus pallidus internus deep brain stimulation: results from the COMPARE Parkinson disease deep brain stimulation cohort.Neurosurgery · 2011Trial
- The Role of GDNF and NSE in Attention-deficit/Hyperactivity Disorder: The Relationship with Sleep and Eating.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Article
- Article
- Treatment of Obesity Through Glial Cell-Derived Neurotrophic Factor Lipid Nanoparticle Delivery in Mice.Gastro hep advances · 2024Article
- GDNF gene therapy for alcohol use disorder in male non-human primates.Nature medicine · 2023Article
- Article
- Elevated endogenous GDNF induces altered dopamine signalling in mice and correlates with clinical severity in schizophrenia.Molecular psychiatry · 2022Article
- Glucose Stimulates Glial Cell Line-Derived Neurotrophic Factor Gene Expression in Microglia through a GLUT5-Independent Mechanism.International journal of molecular sciences · 2022Article
- Inflammation-related plasma protein levels and association with adiposity measurements in young adults.Scientific reports · 2021Article
- Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease.PLoS genetics · 2021Article
- Failure of Glial Cell-Line Derived Neurotrophic Factor (GDNF) in Clinical Trials Orchestrated By Reduced NR4A2 (NURR1) Transcription Factor in Parkinson's Disease. A Systematic Review.Frontiers in aging neuroscience · 2021Article
- Small Molecules and Peptides Targeting Glial Cell Line-Derived Neurotrophic Factor Receptors for the Treatment of Neurodegeneration.International journal of molecular sciences · 2020Review
- Chronic 2-Fold Elevation of Endogenous GDNF Levels Is Safe and Enhances Motor and Dopaminergic Function in Aged Mice.Molecular therapy. Methods & clinical development · 2020Article
- Lipid rafts and neurodegeneration: structural and functional roles in physiologic aging and neurodegenerative diseases.Journal of lipid research · 2020Review
- The Future of GDNF in Parkinson's Disease.Frontiers in aging neuroscience · 2020Article
- Intranasal Delivery of pGDNF DNA Nanoparticles Provides Neuroprotection in the Rat 6-Hydroxydopamine Model of Parkinson's Disease.Molecular neurobiology · 2019Article
- Two-fold elevation of endogenous GDNF levels in mice improves motor coordination without causing side-effects.Scientific reports · 2018Article
- Immune-evasive gene switch enables regulated delivery of chondroitinase after spinal cord injury.Brain : a journal of neurology · 2018Article
- Rationally Engineered AAV Capsids Improve Transduction and Volumetric Spread in the CNS.Molecular therapy. Nucleic acids · 2017Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Intraventricular administration of glial cell line-derived neurotrophic factor (GDNF) in primate and humans to study Parkinson's disease (PD) has revealed the potential for GDNF to induce weight loss. Our previous data indicate that bilateral continuous hypothalamic GDNF overexpression via recombinant adeno-associated virus (rAAV) results in significant failure to gain weight in young rats and weight loss in aged rats. Based on these previous results, we hypothesized that because the nigrostriatal tract passes through the lateral hypothalamus, motor hyperactivity mediated by nigrostriatal dopamine (DA) may have been responsible for the previously observed effect on body weight. In this study, we compared bilateral injections of rAAV2/5-GDNF in hypothalamus versus substantia nigra (SN) in aged Brown-Norway X Fisher 344 rats. Nigrostriatal GDNF overexpression resulted in significantly greater weight loss than rats treated in hypothalamus. The nigral or hypothalamic GDNF-induced weight loss was unrelated to motor activity levels of the rats, though some of the weight loss could be attributed to a transient reduction in food intake. Forebrain DA levels did not account for the observed effects on body weight, although GDNF-induced increases in nucleus accumbens DA may have partially contributed to this effect in the hypothalamic GDNF-treated group. However, only nigrostriatal GDNF overexpression induced activation of phosphorylated extracellular signal-regulated kinase (p-ERK) in a small population of corticotrophin-releasing factor [corticotrophin-releasing hormone (CRH)] neurons located specifically in the medial parvocellullar division (MPD) of the paraventricular nucleus of the hypothalamus. Activation of these hypothalamic CRH neurons likely accounted for the observed metabolic effects leading to weight loss in obese rats.
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Registered trials
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.