Dual response of BDNF to sublethal concentrations of β-amyloid peptides in cultured cortical neurons

Abstract

Beta-amyloid (Aβ) deposition is one important pathological hallmark in Alzheimer's disease (AD). However, low levels of Aβ may modify critical endogenous protection systems before neurodegeneration occurs. We examined the time-course effect of sublethal concentrations of Aβ on total BDNF (panBDNF), BDNF transcripts (I, II, IV and VI), trkB.FL, trkB.T1 and p75NGFR mRNA expression in cultured cortical neurons. We have shown that Aβ exhibited a dual response on BDNF mRNA, i.e. an increase at short times (3–5 h) and a dramatic decrease at longer times (24 or 48 h). The early increase in BDNF expression seems to be driven by increased expression of transcripts I and IV. The BDNF drop was specific since did not occur for other mRNAs examined. The BDNF protein content showed a similar profile but did not follow the dramatic reduction as its encoding mRNA. These observations may help to explain cognitive deficits observed at initial stages of AD.

Keywords

• Alzheimer's disease
• Cultured cortical neurons
• Beta-amyloids
• BDNF
• proBDNF
• TrkB receptors