scholarly journals Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence

2017 ◽  
Vol 114 (31) ◽  
pp. 8390-8395 ◽  
Author(s):  
Sophie E. Holmes ◽  
Matthew J. Girgenti ◽  
Margaret T. Davis ◽  
Robert H. Pietrzak ◽  
Nicole DellaGioia ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Molecular Mechanisms ◽  
Metabotropic Glutamate Receptor ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate ◽  
Positron Emission ◽  
Positive Correlations ◽  
Human Postmortem Tissue ◽  
Glutamate System

Posttraumatic stress disorder (PTSD) is a prevalent and highly disabling disorder, but there is currently no targeted pharmacological treatment for it. Dysfunction of the glutamate system has been implicated in trauma and stress psychopathology, resulting in a growing interest in modulation of the glutamate system for the treatment of PTSD. Specifically, the metabotropic glutamate receptor 5 (mGluR5) represents a promising treatment target. We used [18F]FPEB, a radioligand that binds to the mGluR5, and positron emission tomography (PET) to quantify in vivo mGluR5 availability in human PTSD vs. healthy control (HCs) subjects. In an independent sample of human postmortem tissue, we investigated expression of proteins that have a functional relationship with mGluR5 and glucocorticoids in PTSD. We observed significantly higher cortical mGluR5 availability in PTSD in vivo and positive correlations between mGluR5 availability and avoidance symptoms. In the postmortem sample, we observed up-regulation of SHANK1, a protein that anchors mGluR5 to the cell surface, as well as decreased expression of FKBP5, implicating aberrant glucocorticoid functioning in PTSD. Results of this study provide insight into molecular mechanisms underlying PTSD and suggest that mGluR5 may be a promising target for mechanism-based treatments aimed at mitigating this disorder.

scholarly journals In vivo variation in same-day estimates of metabotropic glutamate receptor subtype 5 binding using [11C]ABP688 and [18F]FPEB

2016 ◽  
Vol 37 (8) ◽  
pp. 2716-2727 ◽  
Author(s):  
Christine DeLorenzo ◽  
Jean-Dominique Gallezot ◽  
John Gardus ◽  
Jie Yang ◽  
Beata Planeta ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Emission Tomography ◽  
Receptor Subtype ◽  
Metabotropic Glutamate ◽  
Positron Emission ◽  
Absolute Test ◽  
Residual Radioactivity

Positron emission tomography tracers [11C]ABP688 and [18F]FPEB target the metabotropic glutamate receptor subtype 5 providing quantification of the brain glutamatergic system in vivo. Previous [11C]ABP688 positron emission tomography human test–retest studies indicate that, when performed on the same day, significant binding increases are observed; however, little deviation is reported when scans are >7 days apart. Due to the small cohorts examined previously (eight and five males, respectively), we aimed to replicate the same-day test–retest studies in a larger cohort including both males and females. Results confirmed large within-subject binding differences (ranging from −23% to 108%), suggesting that measurements are greatly affected by study design. We further investigated whether this phenomenon was specific to [11C]ABP688. Using [18F]FPEB and methodology that accounts for residual radioactivity from the test scan, four subjects were scanned twice on the same day. In these subjects, binding estimates increased between 5% and 39% between scans. Consistent with [11C]ABP688, mean absolute test–retest variability was previously reported as <12% when scans were >21 days apart. This replication study and pilot extension to [18F]FPEB suggest that observed within-day binding variation may be due to characteristics of mGluR5; for example, diurnal variation in mGluR5 may affect measurement of this receptor.

Sign in / Sign up

Export Citation Format

Share Document