Reduced BDNF mRNA expression in the Parkinson's disease substantia nigra

D. W. Howells, M. J. Porritt, J. Y.F. Wong, P. E. Batchelor, R. Kalnins, A. J. Hughes, G. A. Donnan

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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 ≤ 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 (r2 = 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. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)127-135
Number of pages9
JournalExperimental Neurology
Volume166
Issue number1
DOIs
Publication statusPublished - 1 Jan 2000
Externally publishedYes

Keywords

  • Brain-derived neurotrophic factor
  • Dopaminergic
  • In situ hybridization
  • Parkinson's disease

Cite this

Howells, D. W., Porritt, M. J., Wong, J. Y. F., 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), 127-135. https://doi.org/10.1006/exnr.2000.7483