A new brain-derived neurotrophic factor transcript and decrease in brain-derived neurotrophic factor transcripts 1, 2 and 3 in Alzheimer's disease parietal cortex

J Neurochem. 2002 Sep;82(5):1058-64. doi: 10.1046/j.1471-4159.2002.01030.x.

Abstract

Brain-derived neurotrophic factor (BDNF) supports hippocampal, cortical and basal forebrain cholinergic neurons, which lose function in Alzheimer's disease. In Alzheimer's tissues such as hippocampus and parietal cortex, brain- derived neurotrophic factor mRNA is decreased three- to four-fold compared with controls. However, the molecular mechanism of the down-regulation of BDNF in Alzheimer's disease is unknown. The human brain-derived neurotrophic factor gene has multiple promoters governing six non-coding upstream exons that are spliced to one downstream coding exon, leading to six different transcripts. Here we report an alternate human splice variant within exon 4I for a total of seven transcripts. Previous brain-derived neurotrophic factor mRNA measurements in Alzheimer's disease tissue were done using the downstream coding exon present in all transcripts. Using RT-PCR primers specific for each upstream exon, we observe a significant decrease in three human brain-derived neurotrophic factor mRNA transcripts in Alzheimer's disease samples compared with controls. Transcripts 1 and 3 each exhibit a two-fold decrease, and transcript 2 shows a five-fold decrease. There are no significant differences between control and Alzheimer's disease samples for the other transcripts, including the new splice variant. In rat, both transcripts 1 and 3 are regulated through the transcription factor cAMP response element binding protein, whose phosphorylation is decreased in the Alzheimer's disease brain. This could lead to specific down-regulation of the brain-derived neurotrophic factor transcripts shown here.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alternative Splicing
  • Alzheimer Disease / metabolism*
  • Base Sequence
  • Brain-Derived Neurotrophic Factor / genetics*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Exons / genetics
  • Female
  • Humans
  • Male
  • Molecular Sequence Data
  • Parietal Lobe / chemistry
  • Parietal Lobe / metabolism*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Brain-Derived Neurotrophic Factor
  • RNA, Messenger