Modulation of nigrostriatal dopaminergic transmission by antisense oligodeoxynucleotide against brain-derived neurotrophic factor

Yuen Sum Lau, Ruyi Hao, Yiu K. Fung, Liu Song Fu, John F. Bishop, Ronald F. Pfeiffer, M. Maral Mouradian

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Brain-derived neurotrophic factor (BDNF) promotes the differentiation and growth of developing dopamine (DA) neurons and supports the survival of mature DA cells in culture. However, the neurotrophic role of endogenous BDNF in the adult DA system in vivo has not been well established. To investigate the hypothesis that blockade of endogenous BDNF expression results in DA dysregulation, we used an 18-mer antisense oligodeoxynucleotide (ODN) targeted to the first ATG codon of the BDNF transcript. The biological activity of the antisense ODN was initially tested in vitro. In cultured dopaminergic MES 23.5 cells, antisense BDNF (20 μM) effectively reduced BDNF protein expression and cell survival. Furthermore, in primary embryonic mesencephalic cultures, antisense BDNF reduced the number of tyrosine hydroxylase positive neurons and inhibited [3H]DA uptake in a time- and dose-dependent manner. The specificity of the antisense molecule was confirmed by comparing its effects with those of a control ODN having the same base composition but in scrambled sequence. In rats, two days following an intranigral or intrastriatal injection of antisense BDNF (0.5 μg), we observed a two-fold and five-fold increase in nigral DA levels, respectively, but no change in striatal DA content. Seven days after an intrastriatal antisense BDNF injection, DA levels were elevated in the striatum apparently due to decreased DA turnover. These observations suggest that inhibition of endogenous BDNF expression tends to augment rather than inhibit nigrostriatal DA transmission. Thus, the biological effects of endogenous BDNF on the nigrostriatal DA system in the adult organism merits further investigation.

Original languageEnglish (US)
Pages (from-to)525-532
Number of pages8
JournalNeurochemical Research
Issue number4
StatePublished - 1998
Externally publishedYes


  • Antisense oligodeoxynucleotide
  • Brain-derived neurotrophic factor
  • Dopaminergic transmission
  • Rat
  • Striatum
  • Susbtantia nigra pars compacta

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Modulation of nigrostriatal dopaminergic transmission by antisense oligodeoxynucleotide against brain-derived neurotrophic factor'. Together they form a unique fingerprint.

Cite this