NGF but not BDNF overexpression protects hippocampal LTP from beta-amyloid-induced impairment

• A twofold increase of NGF and BDNF concentrations was obtained in the hippocampus using lentiviral gene transfer.
• 50 nM Aβ (25–35) was chosen for modeling of pathological conditions and hippocampal LTP impairment.
• NGF overexpression protects hippocampal LTP from Aβ-induced impairment, while BDNF overexpression does not.
• Blockade of PI3K signaling cascade by LY294002 inhibitor abolishes the neuroprotective effect of NGF.

Two major neurotrophic factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are involved in a number of physiological processes associated with neuronal growth, survival and plasticity. There are an increasing number of papers demonstrating their ability to serve as neuroprotective molecules under various pathological conditions. At the same time, it remains unclear whether both NGF and BDNF have similar roles under pathological conditions and their effects on the electrophysiological properties of neurons after acute pathogen exposure. In the present paper we investigated the neuroprotective role of these two neurotrophins in a well-characterized model of beta-amyloid peptide (Aβ)-dependent impairment of long-term potentiation (LTP). Using lentiviral gene delivery we performed long-term elevation of neurotrophin expression in the dentate gyrus (DG) of rats. One week after virus injection acute brain slices were incubated with beta-amyloid (25–35) for 1 h and afterward in vitro LTP induction was performed in medial perforant path–DG synapses. We demonstrate that chronic elevation of NGF but not BDNF concentration protects LTP induction from beta-amyloid action. Further inhibitory analysis suggests that the effect of NGF is mediated by PI3K-signaling cascade.