TY - JOUR
T1 - Seasonal fluctuations in BDNF regulate hibernation and torpor in golden-mantled ground squirrels
AU - Hernandez, Caterina M.
AU - Florant, Gregory L.
AU - Stranahan, Alexis M.
PY - 2024/4/1
Y1 - 2024/4/1
N2 - Aphagic hibernators such as the golden-mantled ground squirrel (GMGS; Callospermophilus lateralis) can fast for months and exhibit profound seasonal fluctuations in body weight, food intake, and behavior. Brain-derived neurotrophic factor (BDNF) regulates cellular and systemic metabolism via mechanisms that are conserved across mammalian species. In this study, we characterized regional changes in BDNF with hibernation, hypothermia, and seasonal cycle in GMGS. Analysis of BDNF protein concentrations by ELISA revealed overlapping seasonal patterns in the hippocampus and hypothalamus, where BDNF levels were highest in summer and lowest in winter. BDNF is the primary ligand for receptor tyrosine kinase B (TrkB), and BDNF/TrkB signaling in the brain potently regulates energy expenditure. To examine the functional relevance of seasonal variation in BDNF, hibernating animals were injected with the small molecule TrkB agonist 7,8-dihydroxyflavone (DHF) daily for 2 wk. When compared with vehicle, DHF-treated animals exhibited fewer torpor bouts and shorter bout durations. These results suggest that activating BDNF/TrkB disrupts hibernation and raise intriguing questions related to the role of BDNF as a potential regulatory mechanism or downstream response to seasonal changes in body temperature and environment.NEW & NOTEWORTHY Golden-mantled ground squirrels exhibit dramatic seasonal fluctuations in metabolism and can fast for months while hibernating. Brain-derived neurotrophic factor is an essential determinant of cellular and systemic metabolism, and in this study, we characterized seasonal fluctuations in BDNF expression and then administered the small molecule BDNF mimetic 7,8-dihydroxyflavone (DHF) in hibernating squirrels. The results indicate that activating BDNF/TrkB signaling disrupts hibernation, with implications for synaptic homeostasis in prolonged hypometabolic states.
AB - Aphagic hibernators such as the golden-mantled ground squirrel (GMGS; Callospermophilus lateralis) can fast for months and exhibit profound seasonal fluctuations in body weight, food intake, and behavior. Brain-derived neurotrophic factor (BDNF) regulates cellular and systemic metabolism via mechanisms that are conserved across mammalian species. In this study, we characterized regional changes in BDNF with hibernation, hypothermia, and seasonal cycle in GMGS. Analysis of BDNF protein concentrations by ELISA revealed overlapping seasonal patterns in the hippocampus and hypothalamus, where BDNF levels were highest in summer and lowest in winter. BDNF is the primary ligand for receptor tyrosine kinase B (TrkB), and BDNF/TrkB signaling in the brain potently regulates energy expenditure. To examine the functional relevance of seasonal variation in BDNF, hibernating animals were injected with the small molecule TrkB agonist 7,8-dihydroxyflavone (DHF) daily for 2 wk. When compared with vehicle, DHF-treated animals exhibited fewer torpor bouts and shorter bout durations. These results suggest that activating BDNF/TrkB disrupts hibernation and raise intriguing questions related to the role of BDNF as a potential regulatory mechanism or downstream response to seasonal changes in body temperature and environment.NEW & NOTEWORTHY Golden-mantled ground squirrels exhibit dramatic seasonal fluctuations in metabolism and can fast for months while hibernating. Brain-derived neurotrophic factor is an essential determinant of cellular and systemic metabolism, and in this study, we characterized seasonal fluctuations in BDNF expression and then administered the small molecule BDNF mimetic 7,8-dihydroxyflavone (DHF) in hibernating squirrels. The results indicate that activating BDNF/TrkB signaling disrupts hibernation, with implications for synaptic homeostasis in prolonged hypometabolic states.
KW - hibernation
KW - metabolism
KW - neurotrophin
KW - seasonal
KW - torpor
KW - TrkB
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UR - http://www.scopus.com/inward/citedby.url?scp=85188970342&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00186.2023
DO - 10.1152/ajpregu.00186.2023
M3 - Article
C2 - 38344803
AN - SCOPUS:85188970342
SN - 0363-6135
VL - 326
SP - R311-R318
JO - American journal of physiology. Regulatory, integrative and comparative physiology
JF - American journal of physiology. Regulatory, integrative and comparative physiology
IS - 4
ER -