Oligomers of beta-amyloid peptide inhibit BDNF-induced arc expression in cultured cortical Neurons.
The progressive memory loss observed in Alzheimer's disease (AD) is accompanied by an increase in the levels of amyloid-beta peptide (Abeta) and a block of synaptic plasticity. Both synaptic plasticity and memory require changes in the expression of synaptic proteins such as the activity-regulated cytoskeleton-associated protein, Arc (also termed Arg3.1). Using a model of synaptic plasticity in which BDNF increases Arc expression in cultured cortical neurons, we have found that an oligomeric form of Abeta strongly inhibits the BDNF-induced increase of Arc expression. Given that Abeta oligomers are likely to be involved in the synaptic dysfunction and cognitive impairment observed in amyloid depositing mouse models, we hypothesize that inhibition of Arc induction by BDNF contributes to the synaptic and memory deficits at early stages of AD.
Echeverria
Valentine
V
Department of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians & Surgeons. Columbia University, 630 West, 168th St, NY, NY 10032, USA.
Berman
Diego E
DE
Arancio
Ottavio
O
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C092069:activity regulated cytoskeletal-associated protein; C075222:amyloid beta-protein (1-42)