ArticleThe Journal of biological chemistry2013
Castration induces Parkinson disease pathologies in young male mice via inducible nitric-oxide synthase.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 56 citations in OpenAlex.
- Selective inhibition of TLR2 stimulates the maturation of oligodendroglial progenitor cells to oligodendrocytes.NeuroImmune pharmacology and therapeutics · 2026Article
- Castration-induced nigrostriatal deficits are linked to reduced TrkB and loss of mature spines in the dorsal striatum.Frontiers in endocrinology · 2026Article
- Benzoate Drugs for Traumatic Brain Injury.Journal of clinical & experimental immunology · 2026Article
- Corrected Version: IL-12 p40 Monomer is Different from Other IL-12 Family Members to Selectively Inhibit IL-12Rβ1 Internalization and Suppress EAE.Journal of clinical & experimental immunology · 2026Article
- 17β-Trenbolone Exposure Enhances Muscle Activity and Exacerbates Parkinson's Disease Progression in Male Mice.Molecular neurobiology · 2025Article
- Sex and gender differences in the molecular etiology of Parkinson's disease: considerations for study design and data analysis.Biology of sex differences · 2025Review
- Article
- [Androgens and Parkinson's disease: the role in humans and in experiment].Problemy endokrinologii · 2022Review
- Androgens and Parkinson's Disease: A Review of Human Studies and Animal Models.Androgens: clinical research and therapeutics · 2021Review
- Nervonic acid amends motor disorder in a mouse model of Parkinson's disease.Translational neuroscience · 2021Article
- Androgen Therapy in Neurodegenerative Diseases.Journal of the Endocrine Society · 2020Review
- The Role of Sex and Sex Hormones in Neurodegenerative Diseases.Endocrine reviews · 2020Review
- Article
- Epalrestat improves motor symptoms by reducing oxidative stress and inflammation in the reserpine induced mouse model of Parkinson's disease.Animal models and experimental medicine · 2020Article
- Sex and the dopaminergic system: Insights from addiction studies.Handbook of clinical neurology · 2020Review
- MicroRNA-326 Inhibits Apoptosis and Promotes Proliferation of Dopaminergic Neurons in Parkinson's Disease Through Suppression of KLK7-Mediated MAPK Signaling Pathway.Journal of molecular neuroscience : MN · 2019Article
- Translocator Protein Ligand Protects against Neurodegeneration in the MPTP Mouse Model of Parkinsonism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Telmisartan Ameliorates Astroglial and Dopaminergic Functions in a Mouse Model of Chronic Parkinsonism.Neurotoxicity research · 2018Article
- Sex: A Significant Risk Factor for Neurodevelopmental and Neurodegenerative Disorders.Brain sciences · 2018Review
- Dopamine induces soluble α-synuclein oligomers and nigrostriatal degeneration.Nature neuroscience · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
Although Parkinson disease (PD) is a progressive neurodegenerative disorder, available animal models do not exhibit irreversible neurodegeneration, and this is a major obstacle in finding out an effective drug against this disease. Here we delineate a new irreversible model to study PD pathogenesis. The model is based on simple castration of young male mice. Levels of inducible nitric-oxide synthase (iNOS), glial markers (glial fibrillary acidic protein and CD11b), and α-synuclein were higher in nigra of castrated male mice than normal male mice. On the other hand, after castration, the level of glial-derived neurotrophic factor (GDNF) markedly decreased in the nigra of male mice. Accordingly, castration also induced the loss of tyrosine hydroxylase-positive neurons in the nigra and decrease in tyrosine hydroxylase-positive fibers and neurotransmitters in the striatum. Reversal of nigrostriatal pathologies in castrated male mice by subcutaneous implantation of 5α-dihydrotestosterone pellets validates an important role of male sex hormone in castration-induced nigrostriatal pathology. Interestingly, castration was unable to cause glial activation, decrease nigral GDNF, augment the death of nigral dopaminergic neurons, induce the loss of striatal fibers, and impair neurotransmitters in iNOS(-/-) male mice. Furthermore, we demonstrate that iNOS-derived NO is responsible for decreased expression of GDNF in activated astrocytes. Together, our results suggest that castration induces nigrostriatal pathologies via iNOS-mediated decrease in GDNF. These results are important because castrated young male mice may be used as a simple, toxin-free, and nontransgenic animal model to study PD-related nigrostriatal pathologies, paving the way for easy drug screening against PD.
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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.