title: Lentiviral-mediated overexpression of nerve growth factor (NGF) prevents beta-amyloid [25-35]-induced long term potentiation (LTP) decline in the rat hippocampus.
abstract: We have explored the potential neuroprotective effect of local lentiviraly-mediated overexpression of nerve growth factor (NGF) on in vivo long-term potentiation (LTP) in the rat hippocampus under pathological conditions. The suspension of lentiviral particles was prepared using a genetic construct containing the human NGF gene under the control of a neuron-specific CaMKII promoter. Two weeks after the viral injection NGF concentration in the hippocampus doubled. In vivo recordings of total electrical activity in the dentate gyrus were performed. While the increased expression of NGF did not affect the amplitude of evoked postsynaptic potentials recorded after a high-frequency stimulation of the perforant path, it prevented the LTP decline induced by the i.c.v. administration of 50 nM beta-amyloid (25-35) 1h prior to tetanization. Our results demonstrate that increased endogenous NGF concentration can rescue hippocampal neuronal function from beta-amyloid peptide induced impairment.
authors.affiliation: Laboratory of Neurophysiology of Learning, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia.
authors.forename: Shukhrat S
authors.initials: SS
authors.lastname: Uzakov
authors.affiliation: Laboratory of Neurophysiology of Learning, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia. Electronic address: ivanov.andre.d@gmail.com.
authors.forename: Andrey D
authors.initials: AD
authors.lastname: Ivanov
authors.affiliation: Laboratory of Molecular Neurobiology, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia.
authors.forename: Sergey 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, Moscow 117485, Russia.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Markevich
authors.affiliation: Laboratory of Functional Biochemistry of Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Gulyaeva
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D057809:HEK293 Cells; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000235:genetics; D008297:Male; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014161:Transduction, Genetic
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D020932:Nerve Growth Factor; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Beta-amyloid; Hippocampus; LTP; Lentivirus; NGF; Neurotrophins; Plasticity