PMID- 30585393
OWN - NLM
STAT- MEDLINE
DCOM- 20200420
LR  - 20240411
IS  - 1474-9726 (Electronic)
IS  - 1474-9718 (Print)
IS  - 1474-9718 (Linking)
VI  - 18
IP  - 2
DP  - 2019 Apr
TI  - Hypothalamic gene transfer of BDNF promotes healthy aging in mice.
PG  - e12846
LID - 10.1111/acel.12846 [doi]
LID - e12846
AB  - 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.
CI  - (c) 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley 
      & Sons Ltd.
FAU - McMurphy, Travis
AU  - McMurphy T
AD  - Department of Cancer Biology and Genetics, College of Medicine, The Ohio State 
      University, Columbus, Ohio.
AD  - The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
FAU - Huang, Wei
AU  - Huang W
AD  - Department of Cancer Biology and Genetics, College of Medicine, The Ohio State 
      University, Columbus, Ohio.
AD  - The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
FAU - Liu, Xianglan
AU  - Liu X
AD  - Department of Cancer Biology and Genetics, College of Medicine, The Ohio State 
      University, Columbus, Ohio.
AD  - The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
FAU - Siu, Jason J
AU  - Siu JJ
AD  - Department of Cancer Biology and Genetics, College of Medicine, The Ohio State 
      University, Columbus, Ohio.
AD  - The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
FAU - Queen, Nicholas J
AU  - Queen NJ
AD  - Department of Cancer Biology and Genetics, College of Medicine, The Ohio State 
      University, Columbus, Ohio.
AD  - The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
FAU - Xiao, Run
AU  - Xiao R
AD  - Department of Cancer Biology and Genetics, College of Medicine, The Ohio State 
      University, Columbus, Ohio.
AD  - The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
FAU - Cao, Lei
AU  - Cao L
AUID- ORCID: 0000-0003-0322-4985
AD  - Department of Cancer Biology and Genetics, College of Medicine, The Ohio State 
      University, Columbus, Ohio.
AD  - The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
LA  - eng
GR  - R01 CA163640/CA/NCI NIH HHS/United States
GR  - R01 CA166590/CA/NCI NIH HHS/United States
GR  - R21 CA178227/CA/NCI NIH HHS/United States
GR  - R01 AG041250/AG/NIA NIH HHS/United States
GR  - R56 AG041250/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20181226
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (Bdnf protein, mouse)
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Female
MH  - *Healthy Aging
MH  - Hypothalamus/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
PMC - PMC6413658
OTO - NOTNLM
OT  - BDNF
OT  - adipose tissue
OT  - aging
OT  - gene transfer
OT  - hypothalamus
OT  - steatosis
EDAT- 2018/12/27 06:00
MHDA- 2020/04/21 06:00
PMCR- 2019/04/01
CRDT- 2018/12/27 06:00
PHST- 2018/05/11 00:00 [received]
PHST- 2018/08/15 00:00 [revised]
PHST- 2018/09/02 00:00 [accepted]
PHST- 2018/12/27 06:00 [pubmed]
PHST- 2020/04/21 06:00 [medline]
PHST- 2018/12/27 06:00 [entrez]
PHST- 2019/04/01 00:00 [pmc-release]
AID - ACEL12846 [pii]
AID - 10.1111/acel.12846 [doi]
PST - ppublish
SO  - Aging Cell. 2019 Apr;18(2):e12846. doi: 10.1111/acel.12846. Epub 2018 Dec 26.