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

The oligomeric form of the amyloid peptide Aβ(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 (Aβ)-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 Aβ(1-42)-treated slices; BDNF protection was mediated by TrkB receptor as assessed by using the tyrosine kinase inhibitor K252a (200 nM). We also investigated the function of endogenous BDNF using a soluble form of TrkB receptor (TrkB IgG). Incubation of slices with TrkB IgG (1 μg/mL) increased the EC vulnerability to Aβ. 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 Aβ(1-42). We found that Aβ induces p38 MAPK phosphorylation, although pretreatment with BDNF prevented Aβ-dependent p38 MAPK phosphorylation. This result was confirmed by an immunoassay in tissue extracts from EC slices collected after electrophysiology.