Influence of alcoholism and cholesterol on TSPO binding in brain: PET [11 C]PBR28 studies in humans and rodents

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Sung Won KimNora D Volkow

Abstract

Neuroinflammation appears to contribute to neurotoxicity observed with heavy alcohol consumption. To assess whether chronic alcohol results in neuroinflammation we used PET and [11C]PBR28, a ligand that binds to the 18-kDa translocator protein (TSPO), to compare participants with an alcohol use disorder (AUD: n = 19) with healthy controls (HC: n = 17), and alcohol-dependent (n = 9) with -nondependent rats (n = 10). Because TSPO is implicated in cholesterol's transport for steroidogenesis, we investigated whether plasma cholesterol levels influenced [11C]PBR28 binding. [11C]PBR28 binding did not differ between AUD and HC. However, when separating by TSPO genotype rs6971, we showed that medium-affinity binders AUD participants showed lower [11C]PBR28 binding than HC in regions of interest (whole brain, gray and white matter, hippocampus, and thalamus), but no group differences were observed in high-affinity binders. Cholesterol levels inversely correlated with brain [11C]PBR28 binding in combined groups, due to a correlation in AUD participants. In rodents, we observed no differences in brain [11C]PBR28 uptake between alcohol-dependent and -nondependent rats. These findings, which are consistent with two previous [11C]PBR28 PET s...Continue Reading

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Citations

Jun 5, 2019·Psychopharmacology·Luana Martins de CarvalhoNora D Volkow
Mar 29, 2019·Psychopharmacology·Ismene L PetrakisMehmet Sofuoglu
Sep 26, 2020·CNS Drugs·Ayushi Anna DineshAnthony C Vernon
Sep 19, 2019·JAMA Psychiatry·Tania Da SilvaRomina Mizrahi
Aug 1, 2019·European Journal of Nuclear Medicine and Molecular Imaging·Jouni TuiskuSimon Cervenka
Oct 28, 2020·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Linda ChangJohnny J He
Nov 21, 2020·Brain and Behavior·Luana Martins De CarvalhoNora D Volkow
Jan 10, 2021·Antioxidants·Pamela J UrrutiaMarco Tulio Núñez
Jul 19, 2020·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Gjertrud L LaurellMartin Schain
Mar 9, 2021·Brain Plasticity·Ignatius Alvarez CooperSelena E Bartlett
May 4, 2021·Brain Communications·Vanessa Di CataldoEmmanuelle Canet-Soulas
May 28, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Claire Leroy, Wadad Saba
Aug 14, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Fabien ChauveauHervé Boutin
Aug 17, 2021·Brain Communications·Anastasia LanquetinAnne-Lise Pitel
Aug 31, 2021·Biological Psychiatry·Tania Da SilvaRomina Mizrahi
Jul 18, 2019·Molecular Neuropsychiatry·Eric A WoodcockKelly P Cosgrove

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Methods Mentioned

BETA
blood draws

Software Mentioned

PXMOD
functional software library ( FSL )
PKIN
PMOD
SPSS
FreeSurfer

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