Hypothalamic gene transfer of BDNF promotes healthy aging

The aging process and age-related diseases all involve metabolic decline and impaired ability to cope with adversity. Environmental enrichment (EE)-a housing environment which recapitulates aspects of active lifestyle-exerts a wide range of health benefits in laboratory rodents. Brain-derived neurot...

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Bibliographic Details
Published inVitamins and hormones Vol. 115; p. 39
Main Authors Cao, Lei, Ali, Seemaab, Queen, Nicholas J
Format Journal Article
LanguageEnglish
Published United States 2021
Subjects
Adipose Tissue - metabolism
Animals
Brain-Derived Neurotrophic Factor - genetics
Brain-Derived Neurotrophic Factor - metabolism
Gene Transfer Techniques
Healthy Aging
Hypothalamus
Mice
Obesity - genetics
Obesity - metabolism
Obesity - therapy
rAAV
Obesity
Adipose tissue
Gene transfer
BDNF
Environmental enrichment
Aging
Healthspan
Hypothalamus
Lifespan
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Summary:The aging process and age-related diseases all involve metabolic decline and impaired ability to cope with adversity. Environmental enrichment (EE)-a housing environment which recapitulates aspects of active lifestyle-exerts a wide range of health benefits in laboratory rodents. Brain-derived neurotrophic factor (BDNF) in the hypothalamus orchestrates autonomic and neuroendocrine processes, serving as one key brain mediator of EE-induced resistance to obesity, cancer, and autoimmunity. Recombinant adeno-associated virus (AAV)-mediated hypothalamic BDNF gene transfer alleviates obesity, diabetes, and metabolic syndromes in both diet-induced and genetic models. One recent study by our lab demonstrates the efficacy and safety of a built-in autoregulatory system to control transgene BDNF expression, mimicking the body's natural feedback systems in middle-age mice. Twelve-month old mice were treated with autoregulatory BDNF vector and monitored for 7months. BDNF gene transfer prevented age-associated metabolic decline by: reducing adiposity, preventing 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. Furthermore, BDNF treatment reduced anxiety-like and depression-like behaviors. This chapter summarizes this work and discusses potential roles that hypothalamic BDNF might play in promoting healthy aging.
ISSN:0083-6729
DOI:10.1016/bs.vh.2020.12.003