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Hypothalamic gene transfer of BDNF promotes healthy aging in mice

The aging process and age‐related diseases all involve perturbed energy adaption and impaired ability to cope with adversity. Brain‐derived neurotrophic factor (BDNF) in the hypothalamus plays important role in regulation of energy balance. Our previous studies show that recombinant adeno‐associated...

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Autores principales: McMurphy, Travis, Huang, Wei, Liu, Xianglan, Siu, Jason J., Queen, Nicholas J., Xiao, Run, Cao, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413658/
https://www.ncbi.nlm.nih.gov/pubmed/30585393
http://dx.doi.org/10.1111/acel.12846
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author McMurphy, Travis
Huang, Wei
Liu, Xianglan
Siu, Jason J.
Queen, Nicholas J.
Xiao, Run
Cao, Lei
author_facet McMurphy, Travis
Huang, Wei
Liu, Xianglan
Siu, Jason J.
Queen, Nicholas J.
Xiao, Run
Cao, Lei
author_sort McMurphy, Travis
collection PubMed
description The aging process and age‐related diseases all involve perturbed energy adaption and impaired ability to cope with adversity. Brain‐derived neurotrophic factor (BDNF) in the hypothalamus plays important role in regulation of energy balance. Our previous studies show that recombinant adeno‐associated virus (AAV)‐mediated hypothalamic BDNF gene transfer alleviates obesity, diabetes, and metabolic syndromes in both diet‐induced and genetic models. Here we examined the efficacy and safety of a built‐in autoregulatory system to control transgene BDNF expression mimicking the body's natural feedback systems in middle‐aged mice. Twelve‐month‐old mice were treated with either autoregulatory BDNF vector or yellow fluorescence protein (YFP) control, maintained on normal diet, and monitored for 28 weeks. BDNF gene transfer prevented the development of aging‐associated metabolic declines characterized by: preventing aging‐associated weight gain, reducing adiposity, reversing the decline of brown fat activity, increasing adiponectin while reducing leptin and insulin in circulation, improving glucose tolerance, increasing energy expenditure, alleviating hepatic steatosis, and suppressing inflammatory genes in the hypothalamus and adipose tissues. Moreover, BDNF treatment reduced anxiety‐like and depression‐like behaviors. These safety and efficacy data provide evidence that hypothalamic BDNF is a target for promoting healthy aging.
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spelling pubmed-64136582019-04-01 Hypothalamic gene transfer of BDNF promotes healthy aging in mice McMurphy, Travis Huang, Wei Liu, Xianglan Siu, Jason J. Queen, Nicholas J. Xiao, Run Cao, Lei Aging Cell Original Papers The aging process and age‐related diseases all involve perturbed energy adaption and impaired ability to cope with adversity. Brain‐derived neurotrophic factor (BDNF) in the hypothalamus plays important role in regulation of energy balance. Our previous studies show that recombinant adeno‐associated virus (AAV)‐mediated hypothalamic BDNF gene transfer alleviates obesity, diabetes, and metabolic syndromes in both diet‐induced and genetic models. Here we examined the efficacy and safety of a built‐in autoregulatory system to control transgene BDNF expression mimicking the body's natural feedback systems in middle‐aged mice. Twelve‐month‐old mice were treated with either autoregulatory BDNF vector or yellow fluorescence protein (YFP) control, maintained on normal diet, and monitored for 28 weeks. BDNF gene transfer prevented the development of aging‐associated metabolic declines characterized by: preventing aging‐associated weight gain, reducing adiposity, reversing the decline of brown fat activity, increasing adiponectin while reducing leptin and insulin in circulation, improving glucose tolerance, increasing energy expenditure, alleviating hepatic steatosis, and suppressing inflammatory genes in the hypothalamus and adipose tissues. Moreover, BDNF treatment reduced anxiety‐like and depression‐like behaviors. These safety and efficacy data provide evidence that hypothalamic BDNF is a target for promoting healthy aging. John Wiley and Sons Inc. 2018-12-26 2019-04 /pmc/articles/PMC6413658/ /pubmed/30585393 http://dx.doi.org/10.1111/acel.12846 Text en © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Papers
McMurphy, Travis
Huang, Wei
Liu, Xianglan
Siu, Jason J.
Queen, Nicholas J.
Xiao, Run
Cao, Lei
Hypothalamic gene transfer of BDNF promotes healthy aging in mice
title Hypothalamic gene transfer of BDNF promotes healthy aging in mice
title_full Hypothalamic gene transfer of BDNF promotes healthy aging in mice
title_fullStr Hypothalamic gene transfer of BDNF promotes healthy aging in mice
title_full_unstemmed Hypothalamic gene transfer of BDNF promotes healthy aging in mice
title_short Hypothalamic gene transfer of BDNF promotes healthy aging in mice
title_sort hypothalamic gene transfer of bdnf promotes healthy aging in mice
topic Original Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413658/
https://www.ncbi.nlm.nih.gov/pubmed/30585393
http://dx.doi.org/10.1111/acel.12846
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