Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons

Porritt, M.J.; Batchelor, P.E.; Howells, D.W

doi:10.1016/j.expneurol.2004.11.030

Cited by 135Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNerve injury and regeneration

Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons

Porritt, M.J., Batchelor, P.E., Howells, D.W·2005·Experimental Neurology

DOI 10.1016/j.expneurol.2004.11.030

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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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A decrease in expression of neurotrophins, especially BDNF, observed in aging and neurodegenerative diseases may contribute to degeneration and death of neurons.
“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]
BDNF has an important role in neuronal survival.
“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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Reduced BDNF mRNA Expression in the Parkinson's Disease Substantia Nigra
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Self-citation
Effects of Brain derived neurotrophic factor (BDNF) on substantial nigra dopaminergic neurons in Parkinson dis- ease rats
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Authors: Porritt, M. J., Batchelor, P. E., & Howells, D. W.
Affiliations: The University of Melbourne (AU)
Corresponding author: Howells, D.W
ORCID: Porritt, M.J.
Batchelor, P.E.
Howells, D.W
Venue: Experimental Neurology
Publisher: Elsevier BV
Published: 2005-03
Volume: 192
Issue: 1
Pages: 226-234
ISSN: 0014-4886 (ISSN-L)
DOI: 10.1016/j.expneurol.2004.11.030
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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 › Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons

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