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Reduced BDNF mRNA expression in the Parkinson's disease substantia nigra.
Exp Neurol. 2000 Nov; 166(1):127-35.EN

Abstract

Brain-derived neurotrophic factor (BDNF) has potent effects on survival and morphology of dopaminergic neurons and thus its loss could contribute to death of these cells in Parkinson's disease (PD). In situ hybridization revealed that BDNF mRNA is strongly expressed by dopaminergic neurons in control substantia nigra pars compacta (SNpc). In clinically and neuropathologically typical PD, SNpc BDNF mRNA expression is reduced by 70% (P = 0.001). This reduction is due, in part, to loss of dopaminergic neurons which express BDNF. However, surviving dopaminergic neurons in the PD SNpc also expressed less BDNF mRNA (20%, P = 0.02) than their normal counterparts. Moreover, while 15% of control neurons had BDNF mRNA expression >1 SD below the control mean, twice as many (28%) of the surviving PD SNpc dopaminergic neurons had BDNF mRNA expression below this value. This 13% difference in proportions (95% CI 8-17%, P < or = 0.000001) indicates the presence of a subset of neurons in PD with particularly low BDNF mRNA expression. Moreover, both control and PD neurons displayed a direct relationship between the density of BDNF mRNA expression per square micrometer of cell surface and neuronal size (r(2) = 0.93, P </= 0.00001) which was lost only in PD neurons expressing the lowest levels of BDNF mRNA. If BDNF is an autocrine/paracrine factor for SNpc dopaminergic neurons, loss of BDNF-expressing neurons may compromise the well-being of their surviving neighbors. Moreover, neurons expressing particularly low levels of BDNF mRNA may be those at greatest risk of injury in PD and possibly the trigger for the degeneration itself.

Authors+Show Affiliations

Department of Medicine, University of Melbourne, Heidelberg, Victoria, 3084, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11031089

Citation

Howells, D W., et al. "Reduced BDNF mRNA Expression in the Parkinson's Disease Substantia Nigra." Experimental Neurology, vol. 166, no. 1, 2000, pp. 127-35.
Howells DW, Porritt MJ, Wong JY, et al. Reduced BDNF mRNA expression in the Parkinson's disease substantia nigra. Exp Neurol. 2000;166(1):127-35.
Howells, D. W., Porritt, M. J., Wong, J. Y., Batchelor, P. E., Kalnins, R., Hughes, A. J., & Donnan, G. A. (2000). Reduced BDNF mRNA expression in the Parkinson's disease substantia nigra. Experimental Neurology, 166(1), 127-35.
Howells DW, et al. Reduced BDNF mRNA Expression in the Parkinson's Disease Substantia Nigra. Exp Neurol. 2000;166(1):127-35. PubMed PMID: 11031089.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced BDNF mRNA expression in the Parkinson's disease substantia nigra. AU - Howells,D W, AU - Porritt,M J, AU - Wong,J Y, AU - Batchelor,P E, AU - Kalnins,R, AU - Hughes,A J, AU - Donnan,G A, PY - 2000/10/14/pubmed PY - 2001/2/28/medline PY - 2000/10/14/entrez SP - 127 EP - 35 JF - Experimental neurology JO - Exp Neurol VL - 166 IS - 1 N2 - Brain-derived neurotrophic factor (BDNF) has potent effects on survival and morphology of dopaminergic neurons and thus its loss could contribute to death of these cells in Parkinson's disease (PD). In situ hybridization revealed that BDNF mRNA is strongly expressed by dopaminergic neurons in control substantia nigra pars compacta (SNpc). In clinically and neuropathologically typical PD, SNpc BDNF mRNA expression is reduced by 70% (P = 0.001). This reduction is due, in part, to loss of dopaminergic neurons which express BDNF. However, surviving dopaminergic neurons in the PD SNpc also expressed less BDNF mRNA (20%, P = 0.02) than their normal counterparts. Moreover, while 15% of control neurons had BDNF mRNA expression >1 SD below the control mean, twice as many (28%) of the surviving PD SNpc dopaminergic neurons had BDNF mRNA expression below this value. This 13% difference in proportions (95% CI 8-17%, P < or = 0.000001) indicates the presence of a subset of neurons in PD with particularly low BDNF mRNA expression. Moreover, both control and PD neurons displayed a direct relationship between the density of BDNF mRNA expression per square micrometer of cell surface and neuronal size (r(2) = 0.93, P </= 0.00001) which was lost only in PD neurons expressing the lowest levels of BDNF mRNA. If BDNF is an autocrine/paracrine factor for SNpc dopaminergic neurons, loss of BDNF-expressing neurons may compromise the well-being of their surviving neighbors. Moreover, neurons expressing particularly low levels of BDNF mRNA may be those at greatest risk of injury in PD and possibly the trigger for the degeneration itself. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/11031089/Reduced_BDNF_mRNA_expression_in_the_Parkinson's_disease_substantia_nigra_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(00)97483-1 DB - PRIME DP - Unbound Medicine ER -