BDNF prevents amyloid-dependent impairment of LTP in the entorhinal cortex by attenuating p38 MAPK phosphorylation

The oligomeric form of the amyloid peptide A?1-42 is capable of perturbing synaptic plasticity in different brain areas. Here, we evaluated the protective role of brain-derived neurotrophic factor (BDNF) in beta amyloid (A?)-dependent impairment of long-term potentiation in entorhinal cortex (EC) slices. We found that BDNF (1 ng/mL) supplied by perfusion was able to rescue long-term potentiation in A?1-42-treated slices; BDNF protection was mediated by TrkB receptor as assessed by using the tyrosine kinase inhibitor K252a (200nM). We also investigated the function of endogenous BDNF using a soluble form of TrkB receptor (TrkB IgG). Incubation of slices with TrkB IgG (1?g/mL) increased the EC vulnerability to A?. Finally, we investigated the effect of BDNF on the cell stress-kinase p38 mitogen-activated protein kinase (MAPK) in primary cortical cell cultures exposed to A?1-42. We found that A? induces p38 MAPK phosphorylation, although pretreatment with BDNF prevented A?-dependent p38 MAPK phosphorylation. This result was confirmed by an immunoassay in tissue extracts from EC slices collected after electrophysiology