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Neuroprotective effects of Cerebrolysin in triple repeat Tau transgenic model of Pick’s disease and fronto-temporal tauopathies

BACKGROUND: Tauopathies are a group of neurodegenerative disorders with accumulation of three-repeat (3R) or four-repeat (4R) Tau. While 3R tau is found in Pick’s disease and Alzheimer’s disease (AD), 4R tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and AD. We ha...

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Autores principales: Rockenstein, Edward, Ubhi, Kiren, Mante, Michael, Florio, Jazmin, Adame, Anthony, Winter, Stefan, Brandstaetter, Hemma, Meier, Dieter, Masliah, Eliezer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4662012/
https://www.ncbi.nlm.nih.gov/pubmed/26611895
http://dx.doi.org/10.1186/s12868-015-0218-7
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author Rockenstein, Edward
Ubhi, Kiren
Mante, Michael
Florio, Jazmin
Adame, Anthony
Winter, Stefan
Brandstaetter, Hemma
Meier, Dieter
Masliah, Eliezer
author_facet Rockenstein, Edward
Ubhi, Kiren
Mante, Michael
Florio, Jazmin
Adame, Anthony
Winter, Stefan
Brandstaetter, Hemma
Meier, Dieter
Masliah, Eliezer
author_sort Rockenstein, Edward
collection PubMed
description BACKGROUND: Tauopathies are a group of neurodegenerative disorders with accumulation of three-repeat (3R) or four-repeat (4R) Tau. While 3R tau is found in Pick’s disease and Alzheimer’s disease (AD), 4R tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and AD. We have previously shown that Cerebrolysin™ (CBL), a neuropeptide mixture with neurotrophic effects, ameliorates the pathology in amyloid precursor protein transgenic (tg) mouse model of AD and 4R tau, however it is unclear if CBL ameliorates the deficits and neuropathology in the mouse model of Pick’s disease over expressing 3R tau. RESULTS: Mice expressing 3R tau (L266V and G272V mutations) under the mThy-1 promoter were treated with CBL in two separate groups, the first was 3 months old (treated for 3 months, IP) and the second was 6 months old (treated for 3 months, IP) at the start of the treatment. We found that although the levels of total 3R tau were unchanged, CBL reduced the levels of hyper-phosphorylated tau in both groups of mice. This was accompanied by reduced neurodegenerative pathology in the neocortex and hippocampus in both groups and by improvements in the behavioral deficits in the nest-building test and water maze in the 3–6 month group. CONCLUSION: Taken together these results support the notion that CBL may be beneficial in other taupathy models by reducing the levels of aberrantly phosphorylated tau.
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spelling pubmed-46620122015-11-28 Neuroprotective effects of Cerebrolysin in triple repeat Tau transgenic model of Pick’s disease and fronto-temporal tauopathies Rockenstein, Edward Ubhi, Kiren Mante, Michael Florio, Jazmin Adame, Anthony Winter, Stefan Brandstaetter, Hemma Meier, Dieter Masliah, Eliezer BMC Neurosci Research Article BACKGROUND: Tauopathies are a group of neurodegenerative disorders with accumulation of three-repeat (3R) or four-repeat (4R) Tau. While 3R tau is found in Pick’s disease and Alzheimer’s disease (AD), 4R tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and AD. We have previously shown that Cerebrolysin™ (CBL), a neuropeptide mixture with neurotrophic effects, ameliorates the pathology in amyloid precursor protein transgenic (tg) mouse model of AD and 4R tau, however it is unclear if CBL ameliorates the deficits and neuropathology in the mouse model of Pick’s disease over expressing 3R tau. RESULTS: Mice expressing 3R tau (L266V and G272V mutations) under the mThy-1 promoter were treated with CBL in two separate groups, the first was 3 months old (treated for 3 months, IP) and the second was 6 months old (treated for 3 months, IP) at the start of the treatment. We found that although the levels of total 3R tau were unchanged, CBL reduced the levels of hyper-phosphorylated tau in both groups of mice. This was accompanied by reduced neurodegenerative pathology in the neocortex and hippocampus in both groups and by improvements in the behavioral deficits in the nest-building test and water maze in the 3–6 month group. CONCLUSION: Taken together these results support the notion that CBL may be beneficial in other taupathy models by reducing the levels of aberrantly phosphorylated tau. BioMed Central 2015-11-26 /pmc/articles/PMC4662012/ /pubmed/26611895 http://dx.doi.org/10.1186/s12868-015-0218-7 Text en © Rockenstein et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Rockenstein, Edward
Ubhi, Kiren
Mante, Michael
Florio, Jazmin
Adame, Anthony
Winter, Stefan
Brandstaetter, Hemma
Meier, Dieter
Masliah, Eliezer
Neuroprotective effects of Cerebrolysin in triple repeat Tau transgenic model of Pick’s disease and fronto-temporal tauopathies
title Neuroprotective effects of Cerebrolysin in triple repeat Tau transgenic model of Pick’s disease and fronto-temporal tauopathies
title_full Neuroprotective effects of Cerebrolysin in triple repeat Tau transgenic model of Pick’s disease and fronto-temporal tauopathies
title_fullStr Neuroprotective effects of Cerebrolysin in triple repeat Tau transgenic model of Pick’s disease and fronto-temporal tauopathies
title_full_unstemmed Neuroprotective effects of Cerebrolysin in triple repeat Tau transgenic model of Pick’s disease and fronto-temporal tauopathies
title_short Neuroprotective effects of Cerebrolysin in triple repeat Tau transgenic model of Pick’s disease and fronto-temporal tauopathies
title_sort neuroprotective effects of cerebrolysin in triple repeat tau transgenic model of pick’s disease and fronto-temporal tauopathies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4662012/
https://www.ncbi.nlm.nih.gov/pubmed/26611895
http://dx.doi.org/10.1186/s12868-015-0218-7
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