Dual response of BDNF to sublethal concentrations of beta-amyloid peptides in cultured cortical neurons.
Beta-amyloid (Abeta) deposition is one important pathological hallmark in Alzheimer's disease (AD). However, low levels of Abeta may modify critical endogenous protection systems before neurodegeneration occurs. We examined the time-course effect of sublethal concentrations of Abeta 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 Abeta 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.
Aliaga
E
E
Centro de Neurobiología y Plasticidad del Desarrollo, Departamento de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Gran Bretaña 1111, Playa Ancha, Valparaíso, Chile.
Silhol
M
M
Bonneau
N
N
Maurice
T
T
Arancibia
S
S
Tapia-Arancibia
L
L
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D007118:Immunoassay; D017403:In Situ Hybridization; D009474:Neurons / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D013997:Time Factors
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D010446:Peptide Fragments; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D020813:Receptor, trkB