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- Galmozzi, Andrea, et al.
(författare)
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ThermoMouse : An In Vivo Model to Identify Modulators of UCP1 Expression in Brown Adipose Tissue
- 2014
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 9:5, s. 1584-1593
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Tidskriftsartikel (refereegranskat)abstract
- Obesity develops when energy intake chronically exceeds energy expenditure. Because brown adipose tissue (BAT) dissipates energy in the form of heat, increasing energy expenditure by augmenting BAT-mediated thermogenesis may represent an approach to counter obesity and its complications. The ability of BAT to dissipate energy is dependent on expression of mitochondrial uncoupling protein 1 (UCP1). To facilitate the identification of pharmacological modulators of BAT UCP1 levels, which may have potential as antiobesity medications, we developed a transgenic model in which luciferase activity faithfully mimics endogenous UCP1 expression and its response to physiologic stimuli. Phenotypic screening of a library using cells derived from this model yielded a small molecule that increases UCP1 expression in brown fat cells and mice. Upon adrenergic stimulation, compound-treated mice showed increased energy expenditure. These tools offer an opportunity to identify pharmacologic modulators of UCP1 expression and uncover regulatory pathways that impact BAT-mediated thermogenesis.
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- Sharp, SI, et al.
(författare)
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Cortical serotonin 1A receptor levels are associated with depression in patients with dementia with Lewy bodies and Parkinson's disease dementia
- 2008
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 26:4, s. 330-338
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Serotonin 1A receptors (5-HT<sub>1A</sub>) have not been studied in dementia with Lewy bodies (DLB) or Parkinson’s disease dementia (PDD) patients with depression. <i>Aim:</i> To examine 5-HT<sub>1A</sub> in DLB and PDD postmortem in relation to depression. <i>Methods:</i> [<sup>3</sup>H]8-hydroxy-2-dipropylaminotetralin binding to 5-HT<sub>1A</sub> was determined in temporal cortex (Brodmann areas, BA20 and BA36) from 10 DLB patients, 17 PDD patients and 9 controls. <i>Results:</i> 5-HT<sub>1A</sub> density was significantly higher in BA36 in combined DLB/PDD patients with depression, but was unaltered in BA20. <i>Conclusion: </i>Higher BA36 5-HT<sub>1A</sub> density in PDD and DLB patients than in control is dependent on whether the patient had experienced depression during life, not DLB/PDD diagnosis. A 5-HT<sub>1A</sub> antagonist adjuvant may improve treatment of depression in dementia.
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