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

Beta-amyloid (A beta) deposition is one important pathological hallmark in Alzheimer's disease (AD). However. low levels of A beta may modify critical endogenous protection systems before neurodegeneration occurs. We examined the time-course effect of sublethal concentrations of A beta on total BDNF (panBDNF), BDNF transcripts (I, II, IV and VI). trkB.FL. trkB.T1 and p75(NGFR) mRNA expression in cultured cortical neurons We have shown that A beta 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. (C) 2009 Elsevier Inc. All rights reserved.