Metabotropic glutamate receptor 5 tracer [ 18 F]-FPEB displays increased binding potential in postcentral gyrus and cerebellum of male individuals with autism: a pilot PET study.

Autor: Fatemi SH; 1Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware St SE, MMC 392, Minneapolis, MN 55455 USA.; 2Department of Neuroscience, University of Minnesota Medical School, 321 Church St. SE, Minneapolis, MN 55455 USA., Wong DF; 3The Russell H. Morgan Department of Radiology and Radiological Science, Section of High Resolution Brain PET Imaging, Division of Nuclear Medicine, and Molecular Imaging, The Johns Hopkins School of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD USA.; 4Department of Neurology, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD USA.; 5Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD USA.; 6Department of Neuroscience, Johns Hopkins University, Baltimore, MD USA., Brašić JR; 3The Russell H. Morgan Department of Radiology and Radiological Science, Section of High Resolution Brain PET Imaging, Division of Nuclear Medicine, and Molecular Imaging, The Johns Hopkins School of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD USA., Kuwabara H; 3The Russell H. Morgan Department of Radiology and Radiological Science, Section of High Resolution Brain PET Imaging, Division of Nuclear Medicine, and Molecular Imaging, The Johns Hopkins School of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD USA., Mathur A; 3The Russell H. Morgan Department of Radiology and Radiological Science, Section of High Resolution Brain PET Imaging, Division of Nuclear Medicine, and Molecular Imaging, The Johns Hopkins School of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD USA., Folsom TD; 1Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware St SE, MMC 392, Minneapolis, MN 55455 USA., Jacob S; 1Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware St SE, MMC 392, Minneapolis, MN 55455 USA., Realmuto GM; 1Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware St SE, MMC 392, Minneapolis, MN 55455 USA., Pardo JV; 1Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware St SE, MMC 392, Minneapolis, MN 55455 USA.; Department of Psychiatry, Veterans Affairs Medical Center, 1 Veterans Drive, Minneapolis, MN 55417-2399 USA., Lee S; 1Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware St SE, MMC 392, Minneapolis, MN 55455 USA.
Jazyk: angličtina
Zdroj: Cerebellum & ataxias [Cerebellum Ataxias] 2018 Feb 12; Vol. 5, pp. 3. Date of Electronic Publication: 2018 Feb 12 (Print Publication: 2018).
DOI: 10.1186/s40673-018-0082-1
Abstrakt: Background: Autism is a neurodevelopmental disorder that is first manifested during early childhood. Postmortem experiments have identified significantly elevated expression of metabotropic glutamate receptor 5 (mGluR5) in cerebellar vermis and prefrontal cortex of individuals with autism.
Methods: In the current study we employed the mGluR5 tracer [ 18 F]-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([ 18 F]-FPEB) to quantify mGluR5 binding in vivo in adults with autism vs. healthy controls using positron emission tomography (PET).
Results: We identified significantly higher [ 18 F]-FPEB binding potential in the postcentral gyrus and cerebellum of individuals with autism. There was a significant negative correlation between age and [ 18 F]-FPEB binding potential in the cerebellum but not in the postcentral gyrus. In the precuneus, [ 18 F]-FPEB binding potential correlated positively with the lethargy subscale score for the Aberrant Behavioral Checklist (ABC). In cerebellum, there were significant negative correlations between [ 18 F]-FPEB binding potential and ABC total score, ABC hyperactivity subscale score, and the ABC inappropriate speech subscale score.
Conclusions: These novel findings demonstrate for the first time that mGluR5 binding is altered in critical brain areas of subjects with autism, suggesting abnormal glutamate signaling in these regions. Finally, the correlations between altered [ 18 F]-FPEB binding potential in the cerebellum and precuneus suggest that some autistic symptoms may be influenced by abnormal glutamate signaling.
Competing Interests: All study procedures involving human subjects were approved by the Johns Hopkins University Institutional Review Board (IRB) and all enrolled study subjects signed and dated IRB-approved consent forms.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Databáze: MEDLINE
Externí odkaz: