Matches in SemOpenAlex for { <https://semopenalex.org/work/W2020156360> ?p ?o ?g. }
- W2020156360 endingPage "565" @default.
- W2020156360 startingPage "554" @default.
- W2020156360 abstract "Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are critical components of the neural circuitry controlling appetite and body weight. Diminished BDNF signaling in mice results in severe hyperphagia and obesity. In humans, BDNF haploinsufficiency and the functional Bdnf Val66Met polymorphism have been linked to elevated food intake and body weight. The mechanisms underlying this dysfunction are poorly defined. We demonstrate a chief role of α2δ-1, a calcium channel subunit and thrombospondin receptor, in triggering overeating in mice with central BDNF depletion. We show reduced α2δ-1 cell-surface expression in the BDNF mutant ventromedial hypothalamus (VMH), an energy balance-regulating center. This deficit contributes to the hyperphagia exhibited by BDNF mutant mice because selective inhibition of α2δ-1 by gabapentin infusion into wild-type VMH significantly increases feeding and body weight gain. Importantly, viral-mediated α2δ-1 rescue in BDNF mutant VMH significantly mitigates their hyperphagia, obesity, and liver steatosis and normalizes deficits in glucose homeostasis. Whole-cell recordings in BDNF mutant VMH neurons revealed normal calcium currents but reduced frequency of EPSCs. These results suggest calcium channel-independent effects of α2δ-1 on feeding and implicate α2δ-1-thrombospondin interactions known to facilitate excitatory synapse assembly. Our findings identify a central mechanism mediating the inhibitory effects of BDNF on feeding. They also demonstrate a novel and critical role for α2δ-1 in appetite control and suggest a mechanism underlying weight gain in humans treated with gabapentinoid drugs." @default.
- W2020156360 created "2016-06-24" @default.
- W2020156360 creator A5012358559 @default.
- W2020156360 creator A5020472720 @default.
- W2020156360 creator A5038038199 @default.
- W2020156360 creator A5048258846 @default.
- W2020156360 creator A5049185212 @default.
- W2020156360 creator A5050412390 @default.
- W2020156360 creator A5050667590 @default.
- W2020156360 creator A5055848930 @default.
- W2020156360 date "2014-01-08" @default.
- W2020156360 modified "2023-10-01" @default.
- W2020156360 title "Hypothalamic Dysfunction of the Thrombospondin Receptor α2δ-1 Underlies the Overeating and Obesity Triggered by Brain-Derived Neurotrophic Factor Deficiency" @default.
- W2020156360 cites W1491764882 @default.
- W2020156360 cites W1967718477 @default.
- W2020156360 cites W1970581037 @default.
- W2020156360 cites W1971002481 @default.
- W2020156360 cites W1975862819 @default.
- W2020156360 cites W1975976108 @default.
- W2020156360 cites W1976844911 @default.
- W2020156360 cites W1979722180 @default.
- W2020156360 cites W1980872889 @default.
- W2020156360 cites W1982647461 @default.
- W2020156360 cites W1985662506 @default.
- W2020156360 cites W1988452935 @default.
- W2020156360 cites W1991545156 @default.
- W2020156360 cites W2000209446 @default.
- W2020156360 cites W2003967044 @default.
- W2020156360 cites W2007161557 @default.
- W2020156360 cites W2011072148 @default.
- W2020156360 cites W2011319382 @default.
- W2020156360 cites W2011936975 @default.
- W2020156360 cites W2016902633 @default.
- W2020156360 cites W2017899632 @default.
- W2020156360 cites W2023162470 @default.
- W2020156360 cites W2024406570 @default.
- W2020156360 cites W2027905035 @default.
- W2020156360 cites W2031237895 @default.
- W2020156360 cites W2034197352 @default.
- W2020156360 cites W2038122755 @default.
- W2020156360 cites W2038864225 @default.
- W2020156360 cites W2045374233 @default.
- W2020156360 cites W2050042714 @default.
- W2020156360 cites W2052038494 @default.
- W2020156360 cites W2054491289 @default.
- W2020156360 cites W2058982402 @default.
- W2020156360 cites W2067572657 @default.
- W2020156360 cites W2077512223 @default.
- W2020156360 cites W2082109839 @default.
- W2020156360 cites W2085295826 @default.
- W2020156360 cites W2090477438 @default.
- W2020156360 cites W2091973393 @default.
- W2020156360 cites W2099781923 @default.
- W2020156360 cites W2102918395 @default.
- W2020156360 cites W2103289578 @default.
- W2020156360 cites W2106085993 @default.
- W2020156360 cites W2111038577 @default.
- W2020156360 cites W2115079887 @default.
- W2020156360 cites W2122304769 @default.
- W2020156360 cites W2131545168 @default.
- W2020156360 cites W2136772404 @default.
- W2020156360 cites W2137113565 @default.
- W2020156360 cites W2137993789 @default.
- W2020156360 cites W2147311167 @default.
- W2020156360 cites W2150862512 @default.
- W2020156360 cites W2156587759 @default.
- W2020156360 cites W2157226283 @default.
- W2020156360 cites W2157856213 @default.
- W2020156360 cites W2159692236 @default.
- W2020156360 cites W2161649767 @default.
- W2020156360 cites W2164647222 @default.
- W2020156360 cites W2167864596 @default.
- W2020156360 cites W2341044912 @default.
- W2020156360 cites W4236258414 @default.
- W2020156360 cites W4245118565 @default.
- W2020156360 doi "https://doi.org/10.1523/jneurosci.1572-13.2014" @default.
- W2020156360 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3870936" @default.
- W2020156360 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24403154" @default.
- W2020156360 hasPublicationYear "2014" @default.
- W2020156360 type Work @default.
- W2020156360 sameAs 2020156360 @default.
- W2020156360 citedByCount "23" @default.
- W2020156360 countsByYear W20201563602014 @default.
- W2020156360 countsByYear W20201563602015 @default.
- W2020156360 countsByYear W20201563602016 @default.
- W2020156360 countsByYear W20201563602017 @default.
- W2020156360 countsByYear W20201563602018 @default.
- W2020156360 countsByYear W20201563602019 @default.
- W2020156360 countsByYear W20201563602020 @default.
- W2020156360 countsByYear W20201563602021 @default.
- W2020156360 countsByYear W20201563602023 @default.
- W2020156360 crossrefType "journal-article" @default.
- W2020156360 hasAuthorship W2020156360A5012358559 @default.
- W2020156360 hasAuthorship W2020156360A5020472720 @default.
- W2020156360 hasAuthorship W2020156360A5038038199 @default.
- W2020156360 hasAuthorship W2020156360A5048258846 @default.
- W2020156360 hasAuthorship W2020156360A5049185212 @default.
- W2020156360 hasAuthorship W2020156360A5050412390 @default.