The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons
Abstract
Brain derived neurotrophic factor (BDNF) expression is significantly reduced in the Parkinson's disease substantia nigra. This neurotrophin has potent affects on dopaminergic neuron survival protecting them from the neurotoxins MPTP and 6-hydroxydopamine (6-OHDA) commonly used to create animal models of Parkinson's disease and also promoting dopaminergic axonal sprouting. In this study, we demonstrate that an antisense oligonucleotide infusion (200 nM for 28 days) to prevent BDNF production in the substantia nigra of rats mimics many features of the classical animal models of Parkinson's disease. 62% of antisense treated rats rotate (P < or = 0.05) in response to dopaminergic receptor stimulation by apomorphine. 40% of substantia nigra pars compacta tyrosine hydroxylase immunoreactive neurons are lost (P < or = 0.00001) and dopamine uptake site density measured by (3)H-mazindol autoradiography is reduced by 34% (P < or = 0.005). Loss of haematoxylin and eosin stained nigral neurons is significant (P < or = 0.0001) but less extensive (34%). These observations indicate that loss of BDNF expression leads both to down regulation of the dopaminergic phenotype and to dopaminergic neuronal death. Therefore, reduced BDNF mRNA expression in Parkinson's disease substantia nigra may contribute directly to the death of nigral dopaminergic neurons and the development of Parkinson's disease.
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“It was found that the decrease in expression of NTs, especially BDNF observed in the aging process and in neurodegenerative diseases, may contribute to degeneration and death of neurons [58].”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [58]
In the citing paper
“which suggests that BDNF has an important role in neuronal survival [166].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [166]
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Metadata
- Authors
- Porritt, M. J., Batchelor, P. E., & Howells, D. W.
- Affiliations
- The University of Melbourne (AU)
- Corresponding author
- Howells, D.W
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 192
- Issue
- 1
- Pages
- 226-234
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W1985464631
- Cited by
- 135
- References
- 56
- Citations by year
- 2025: 7 · 2024: 2 · 2023: 7 · 2022: 5 · 2021: 4 · 2020: 8 · 2019: 3 · 2018: 10 · 2017: 9 · 2016: 6 · 2015: 10 · 2014: 5 · 2013: 6 · 2012: 11
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hospital Research Foundation
- Austin Medical Research Foundation
- National Health and Medical Research Council
- National Medical Research Council
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- brain-derived neurotrophic factor, substantia nigra pars compacta, dopaminergic neuron loss, Parkinson's disease, tyrosine hydroxylase, dopamine uptake, MPTP, 6-hydroxydopamine, apomorphine rotation, Parkinson's disease model
- MeSH terms
- Animals, Binding, Competitive, Cell Survival, Disease Models, Animal, Dopamine, Male, Mazindol, Nerve Degeneration, Neurons, Radioligand Assay, Receptors, Dopamine, RNA, Messenger, Substantia Nigra, Tyrosine 3-Monooxygenase, Down-Regulation, Oligonucleotides, Antisense, Cell Death, Rats, Sprague-Dawley, Neuroprotective Agents, Dopamine Uptake Inhibitors, Brain-Derived Neurotrophic Factor, Parkinsonian Disorders, Rats
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