ProNGF\NGF imbalance triggers learning and memory deficits, neurodegeneration and spontaneous epileptic-like discharges in transgenic mice
| Autor: | Rossella Brandi, Sonia Piccinin, Luisa Fasulo, Raffaella Scardigli, Simona Capsoni, Antonino Cattaneo, Francesca Malerba, Gianluca Amato, Annalisa Manca, Fulvio Florenzano, Giovanni Meli, Francesca Paoletti, P Capelli, Robert Nisticò, Sara Marinelli, F La Regina, Cecilia Tiveron, Agnese Lecci, Nicola Berretta, Flaminia Pavone, L. Pistillo, Simona D'Aguanno |
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| Přispěvatelé: | Tiveron, C, Fasulo, L, Capsoni, Simona, Malerba, Francesca, Marinelli, S, Paoletti, Francesca, Piccinin, S, Scardigli, R, Amato, G, Brandi, R, Capelli, Paolo, D'Aguanno, S, Florenzano, F, La Regina, F, Lecci, A, Manca, A, Meli, GIOVANNI ANTONIO, Pistillo, L, Berretta, N, Nistico, R, Pavone, F, Cattaneo, Antonino |
| Rok vydání: | 2013 |
| Předmět: |
Male
Genetically modified mouse Aging medicine.medical_specialty Transgene Socio-culturale Hippocampus Mice Transgenic physiology Animals Behavior Animal physiology Disease Models Animal Epilepsy physiopathology Hippocampus physiopathology Homeostasis physiology Learning Disorders physiopathology Male Memory Disorders physiopathology Mice Mice Inbred C57BL Mice Transgenic Nerve Growth Factor deficiency/genetics/physiology Neurodegenerative Diseases physiopathology Phenotype Protein Precursors deficiency/genetics/physiology Inbred C57BL Transgenic Animals Behavior Animal Disease Models Animal Epilepsy Homeostasis Learning Disorders Memory Disorders Mice Mice Inbred C57BL Nerve Growth Factor Neurodegenerative Diseases Phenotype Protein Precursors Internal medicine medicine Amyloid precursor protein Molecular Biology Original Paper Behavior biology Learning Disabilities Neurodegeneration Settore BIO/14 Cell Biology medicine.disease Endocrinology Nerve growth factor physiology Disease Models biology.protein Cholinergic physiopathology Neuroscience Neurotrophin |
| Zdroj: | Cell death and differentiation (Online) Epub ahead of print (2013). doi:10.1038/cdd.2013.22 info:cnr-pdr/source/autori:Tiveron C, Fasulo L, Capsoni S, Malerba F, Marinelli S, Paoletti F, Piccinin S, Scardigli R, Amato G, Brandi R, Capelli P, D'Aguanno S, Florenzano F, La Regina F, Lecci A, Manca A, Meli G, Pistillo L, Berretta N, Nisticò R, Pavone F, Cattaneo A./titolo:ProNGF\NGF imbalance triggers learning and memory deficits, neurodegeneration and spontaneous epileptic-like discharges in transgenic mice/doi:10.1038%2Fcdd.2013.22/rivista:Cell death and differentiation (Online)/anno:2013/pagina_da:/pagina_a:/intervallo_pagine:/volume:Epub ahead of |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/cdd.2013.22 |
| Popis: | ProNGF, the precursor of mature nerve growth factor (NGF), is the most abundant form of NGF in the brain. ProNGF and mature NGF differ significantly in their receptor interaction properties and in their bioactivity. ProNGF increases markedly in the cortex of Alzheimer's disease (AD) brains and proNGF\NGF imbalance has been postulated to play a role in neurodegeneration. However, a direct proof for a causal link between increased proNGF and AD neurodegeneration is lacking. In order to evaluate the consequences of increased levels of proNGF in the postnatal brain, transgenic mice expressing a furin cleavage-resistant form of proNGF, under the control of the neuron-specific mouse Thy1.2 promoter, were derived and characterized. Different transgenic lines displayed a phenotypic gradient of neurodegenerative severity features. We focused the analysis on the two lines TgproNGF#3 and TgproNGF#72, which shared learning and memory impairments in behavioral tests, cholinergic deficit and increased Aβ-peptide immunoreactivity. In addition, TgproNGF#3 mice developed Aβ oligomer immunoreactivity, as well as late diffuse astrocytosis. Both TgproNGF lines also display electrophysiological alterations related to spontaneous epileptic-like events. The results provide direct evidence that alterations in the proNGF/NGF balance in the adult brain can be an upstream driver of neurodegeneration, contributing to a circular loop linking alterations of proNGF/NGF equilibrium to excitatory/inhibitory synaptic imbalance and amyloid precursor protein (APP) dysmetabolism. |
| Databáze: | OpenAIRE |
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