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Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons.
Exp Neurol. 2005 Mar; 192(1):226-34.EN

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.

Authors+Show Affiliations

Department of Medicine, University of Melbourne, Level 7, Lance Townsend Building, Austin Health, Studley Road, Heidelberg, Vic 3084 Australia.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15698637

Citation

Porritt, M J., et al. "Inhibiting BDNF Expression By Antisense Oligonucleotide Infusion Causes Loss of Nigral Dopaminergic Neurons." Experimental Neurology, vol. 192, no. 1, 2005, pp. 226-34.
Porritt MJ, Batchelor PE, Howells DW. Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons. Exp Neurol. 2005;192(1):226-34.
Porritt, M. J., Batchelor, P. E., & Howells, D. W. (2005). Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons. Experimental Neurology, 192(1), 226-34.
Porritt MJ, Batchelor PE, Howells DW. Inhibiting BDNF Expression By Antisense Oligonucleotide Infusion Causes Loss of Nigral Dopaminergic Neurons. Exp Neurol. 2005;192(1):226-34. PubMed PMID: 15698637.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibiting BDNF expression by antisense oligonucleotide infusion causes loss of nigral dopaminergic neurons. AU - Porritt,M J, AU - Batchelor,P E, AU - Howells,D W, PY - 2004/07/16/received PY - 2004/10/27/revised PY - 2004/11/10/accepted PY - 2005/2/9/pubmed PY - 2005/4/15/medline PY - 2005/2/9/entrez SP - 226 EP - 34 JF - Experimental neurology JO - Exp Neurol VL - 192 IS - 1 N2 - 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. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/15698637/Inhibiting_BDNF_expression_by_antisense_oligonucleotide_infusion_causes_loss_of_nigral_dopaminergic_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(04)00449-2 DB - PRIME DP - Unbound Medicine ER -