title: NGF but not BDNF overexpression protects hippocampal LTP from beta-amyloid-induced impairment.
abstract: 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 1h 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.
authors.affiliation: Laboratory of Neurophysiology of Learning, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 5A Butlerova Street, Moscow 117485, Russia. Electronic address: ivanov.andre.d@gmail.com.
authors.forename: A D
authors.initials: AD
authors.lastname: Ivanov
authors.affiliation: Laboratory of Molecular Neurobiology, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 5A Butlerova Street, Moscow 117485, Russia.
authors.forename: G R
authors.initials: GR
authors.lastname: Tukhbatova
authors.affiliation: Laboratory of Molecular Neurobiology, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 5A Butlerova Street, Moscow 117485, Russia.
authors.forename: S V
authors.initials: SV
authors.lastname: Salozhin
authors.affiliation: Laboratory of Neurophysiology of Learning, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 5A Butlerova Street, Moscow 117485, Russia.
authors.forename: V A
authors.initials: VA
authors.lastname: Markevich
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*; D019580:Perforant Pathway / Q000187:drug effects / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011897:Random Allocation; D017208:Rats, Wistar; D046509:Tissue Culture Techniques
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D020932:Nerve Growth Factor; D010446:Peptide Fragments; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C074636:amyloid beta-protein (25-35); C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: BDNF; LTP; NGF; beta-amyloid; neuroprotection; plasticity