title: BDNF prevents amyloid-dependent impairment of LTP in the entorhinal cortex by attenuating p38 MAPK phosphorylation.
abstract: 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.
authors.affiliation: Neuroscience Institute, Italian National Research Council, Pisa, Italy; Department of Applied Clinical Sciences and Biotechnology, University of L'Aquila, Coppito, L'Aquila, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Criscuolo
authors.affiliation: Neuroscience Institute, Italian National Research Council, Pisa, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Fabiani
authors.affiliation: Neuroscience Institute, Italian National Research Council, Pisa, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Bonadonna
authors.affiliation: Neuroscience Institute, Italian National Research Council, Pisa, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Origlia
authors.affiliation: Neuroscience Institute, Italian National Research Council, Pisa, Italy; Department of Applied Clinical Sciences and Biotechnology, University of L'Aquila, Coppito, L'Aquila, Italy. Electronic address: domenici@in.cnr.it.
authors.forename: Luciano
authors.initials: L
authors.lastname: Domenici
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D018728:Entorhinal Cortex / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects; D018696:Neuroprotective Agents; D010446:Peptide Fragments / Q000009:adverse effects*; D010766:Phosphorylation / Q000187:drug effects; D020813:Receptor, trkB / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D020813:Receptor, trkB; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Alzheimer's disease; Neurodegeneration; Neuroprotection; Synaptic plasticity