title: Decreased hippocampal translocator protein (18 kDa) expression in alcohol dependence: a [11C]PBR28 PET study.
abstract: Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [11C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance. Twenty healthy control (HC) subjects (45±13; M:F 14:6) and nine ADP (45±6, M:F 9:0) were evaluated. Dynamic PET data were acquired for 90 min following an injection of 331±15 MBq [11C]PBR28. Regional volumes of distribution (VT) for regions of interest (ROIs) identified a priori were estimated using a two-tissue compartmental model with metabolite-corrected arterial plasma input function. ADP had an ~20% lower [11C]PBR28 VT,in the hippocampus (F(1,24) 5.694; P=0.025), but no difference in VTin other ROIs. Hippocampal [11C]PBR28 VTwas positively correlated with verbal memory performance in a combined group of HC and ADP (r=0.720, P<0.001), an effect seen in HC alone (r=0.738; P=0.001) but not in ADP. We did not find evidence for increased microglial activation in ADP, as seen pre-clinically. Instead, our findings suggest lower glial density or an altered activation state with lower TSPO expression. The correlation between verbal memory and [11C]PBR28 VT, raises the possibility that abnormalities of glial function may contribute to cognitive impairment in ADP.
authors.affiliation: National Addictions Centre, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Kalk
authors.affiliation: Neuroimaging Department, Kings College London, London, UK.|Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: Q
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Division of Brain Sciences, Imperial College London, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Owen
authors.affiliation: West London Mental Health NHS Trust, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Cherian
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Erritzoe
authors.affiliation: Centre for Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
authors.forename: A
authors.initials: A
authors.lastname: Gilmour
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: Ribeiro
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: McGonigle
authors.affiliation: Division of Brain Sciences, Imperial College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Waldman
authors.affiliation: Division of Brain Sciences, Imperial College London, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Matthews
authors.affiliation: Institute of Health and Well-being, University of Glasgow, Glasgow, UK.
authors.forename: J
authors.initials: J
authors.lastname: Cavanagh
authors.affiliation: Centre for Infection, Inflammation and Immunity, University of Glasgow, Glasgow, UK.
authors.forename: I
authors.initials: I
authors.lastname: McInnes
authors.affiliation: Central and North West London NHS Trust, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Dar
authors.affiliation: Imanova Limited, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Gunn
authors.affiliation: Imanova Limited, London, UK.
authors.forename: E A
authors.initials: EA
authors.lastname: Rabiner
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Lingford-Hughes
mesh_terms: D000081:Acetamides; D000437:Alcoholism / Q000000981:diagnostic imaging / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D004340:Drug Contamination; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D008297:Male; D017628:Microglia / Q000378:metabolism*; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011725:Pyridines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA / Q000378:metabolism*
chemical_list: D000081:Acetamides; D002250:Carbon Radioisotopes; C526798:N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide; D011725:Pyridines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human