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Systemic Delivery of Recombinant Brain Derived Neurotrophic Factor (BDNF) in the R6/2 Mouse Model of Huntington’s Disease

Loss of huntingtin-mediated BDNF gene transcription has been shown to occur in HD and thus contribute to the degeneration of the striatum. Several studies have indicated that an increase in BDNF levels is associated with neuroprotection and amelioration of neurological signs in animal models of HD....

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Autores principales: Giampà, Carmela, Montagna, Elena, Dato, Clemente, Melone, Mariarosa A. B., Bernardi, Giorgio, Fusco, Francesca Romana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659095/
https://www.ncbi.nlm.nih.gov/pubmed/23700454
http://dx.doi.org/10.1371/journal.pone.0064037
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author Giampà, Carmela
Montagna, Elena
Dato, Clemente
Melone, Mariarosa A. B.
Bernardi, Giorgio
Fusco, Francesca Romana
author_facet Giampà, Carmela
Montagna, Elena
Dato, Clemente
Melone, Mariarosa A. B.
Bernardi, Giorgio
Fusco, Francesca Romana
author_sort Giampà, Carmela
collection PubMed
description Loss of huntingtin-mediated BDNF gene transcription has been shown to occur in HD and thus contribute to the degeneration of the striatum. Several studies have indicated that an increase in BDNF levels is associated with neuroprotection and amelioration of neurological signs in animal models of HD. In a recent study, an increase in BDNF mRNA and protein levels was recorded in mice administered recombinant BDNF peripherally. Chronic, indwelling osmotic mini-pumps containing either recombinant BDNF or saline were surgically placed in R6/2 or wild-type mice from 4 weeks of age until euthanasia. Neurological evaluation (paw clasping, rotarod performance, locomotor activity in an open field) was performed. After transcardial perfusion, histological and immunohistochemical studies were performed. We found that BDNF- treated R6/2 mice survived longer and displayed less severe signs of neurological dysfunction than the vehicle treated ones. Primary outcome measures such as brain volume, striatal atrophy, size and morphology of striatal neurons, neuronal intranuclear inclusions and microglial reaction confirmed a neuroprotective effect of the compound. BDNF was effective in increasing significantly the levels of activated CREB and of BDNF the striatal spiny neurons. Moreover, systemically administered BDNF increased the synthesis of BDNF as demonstrated by RT-PCR, and this might account for the beneficial effects observed in this model.
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spelling pubmed-36590952013-05-22 Systemic Delivery of Recombinant Brain Derived Neurotrophic Factor (BDNF) in the R6/2 Mouse Model of Huntington’s Disease Giampà, Carmela Montagna, Elena Dato, Clemente Melone, Mariarosa A. B. Bernardi, Giorgio Fusco, Francesca Romana PLoS One Research Article Loss of huntingtin-mediated BDNF gene transcription has been shown to occur in HD and thus contribute to the degeneration of the striatum. Several studies have indicated that an increase in BDNF levels is associated with neuroprotection and amelioration of neurological signs in animal models of HD. In a recent study, an increase in BDNF mRNA and protein levels was recorded in mice administered recombinant BDNF peripherally. Chronic, indwelling osmotic mini-pumps containing either recombinant BDNF or saline were surgically placed in R6/2 or wild-type mice from 4 weeks of age until euthanasia. Neurological evaluation (paw clasping, rotarod performance, locomotor activity in an open field) was performed. After transcardial perfusion, histological and immunohistochemical studies were performed. We found that BDNF- treated R6/2 mice survived longer and displayed less severe signs of neurological dysfunction than the vehicle treated ones. Primary outcome measures such as brain volume, striatal atrophy, size and morphology of striatal neurons, neuronal intranuclear inclusions and microglial reaction confirmed a neuroprotective effect of the compound. BDNF was effective in increasing significantly the levels of activated CREB and of BDNF the striatal spiny neurons. Moreover, systemically administered BDNF increased the synthesis of BDNF as demonstrated by RT-PCR, and this might account for the beneficial effects observed in this model. Public Library of Science 2013-05-20 /pmc/articles/PMC3659095/ /pubmed/23700454 http://dx.doi.org/10.1371/journal.pone.0064037 Text en © 2013 Giampà et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Giampà, Carmela
Montagna, Elena
Dato, Clemente
Melone, Mariarosa A. B.
Bernardi, Giorgio
Fusco, Francesca Romana
Systemic Delivery of Recombinant Brain Derived Neurotrophic Factor (BDNF) in the R6/2 Mouse Model of Huntington’s Disease
title Systemic Delivery of Recombinant Brain Derived Neurotrophic Factor (BDNF) in the R6/2 Mouse Model of Huntington’s Disease
title_full Systemic Delivery of Recombinant Brain Derived Neurotrophic Factor (BDNF) in the R6/2 Mouse Model of Huntington’s Disease
title_fullStr Systemic Delivery of Recombinant Brain Derived Neurotrophic Factor (BDNF) in the R6/2 Mouse Model of Huntington’s Disease
title_full_unstemmed Systemic Delivery of Recombinant Brain Derived Neurotrophic Factor (BDNF) in the R6/2 Mouse Model of Huntington’s Disease
title_short Systemic Delivery of Recombinant Brain Derived Neurotrophic Factor (BDNF) in the R6/2 Mouse Model of Huntington’s Disease
title_sort systemic delivery of recombinant brain derived neurotrophic factor (bdnf) in the r6/2 mouse model of huntington’s disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659095/
https://www.ncbi.nlm.nih.gov/pubmed/23700454
http://dx.doi.org/10.1371/journal.pone.0064037
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