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.
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.
D000368:Aged; D017398:Alternative Splicing; D000544:Alzheimer Disease / Q000378:metabolism*; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010296:Parietal Lobe / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger