Talk abstracts
Talk on Wednesday 03:00-03:15pm submitted by Seemaab Ali
Long-term environmental enrichment improves age-related hypothalamic inflammation and metabolic syndrome in middle-age mice
Seemaab Ali (Neuroscience Graduate Program), Travis B. McMurphy (Biomedical Sciences Graduate Program), Xianglan Liu, Wei Huang, Nicholas J. Queen (Cancer Biology and Genetics), Jason Siu (Neuroscience Grdaute Program), Ripal Patel, Jennifer Saxton (College of Arts and Sciences), Lei Cao (Cancer Biology and Genetics)
Abstract:
Age-related morbidities are a rapidly growing public health concern, but the mechanisms underlying the aging process and its interaction with environment are not completely understood. We use a model of lifestyle improvement called environmental enrichment (EE), which provides mice with novel and complex housing. This model has been shown to produce anti-obesity phenotypes mediated by the hypothalamic-sympathoneural-adipocyte (HSA) axis: brain-derived neurotrophic factor (BDNF) upregulation in the hypothalamus leads to sympathetic activation, which results in adipose browning. The mediobasal hypothalamus was recently identified as a mediator of systemic aging and age-related metabolic syndrome, by increased hypothalamic inflammation. We investigated the role of EE and the HSA axis in normal aging, using 10 month old middle-age mice in EE or standard conditions for short-term (6 weeks) or long-term (8 to 12 months) housing. Short-term EE activated the HSA axis and resulted in reduced adiposity in middle-age mice. Long-term EE for 12 months reduced adiposity without overall weight loss, while improving glucose tolerance and enhancing motor abilities. Long-term EE also significantly reduced hypothalamic expression of inflammatory cytokines and NFκB-related genes. Adeno-associated virus (AAV) genetic delivery of BDNF to the hypothalamus of middle-age mice resulted in the same metabolic improvements, while also downregulating inflammatory genes. Morphological differences in microglia are evident by 8 months of EE and correspond to microglia without age-related dysfunction. Blocking neuronal BDNF signaling in the hypothalamus by AAV delivery of a dominant negative BDNF receptor prevented the anti-obesity benefits of EE out to 6 months, and resulted in robust microglial activation and immune infiltration within the hypothalamus. These data suggest that EE and hypothalamic expression of BDNF reduce age-related hypothalamic inflammation and support healthy aging.
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Keywords: Aging, Enrichment, Microglia