Challenges and rewards of in vivo synaptic density imaging, and its application to the study of depression.

Autor: Asch RH; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA., Abdallah CG; Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA., Carson RE; Department of Radiology and Biomedical Imaging, Yale Positron Emission Tomography Center, Yale School of Medicine, New Haven, CT, USA.; Department of Biomedical Engineering, Yale School of Engineering, New Haven, CT, USA., Esterlis I; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA. irina.esterlis@yale.edu.; Department of Radiology and Biomedical Imaging, Yale Positron Emission Tomography Center, Yale School of Medicine, New Haven, CT, USA. irina.esterlis@yale.edu.; U.S. Department of Veteran Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA. irina.esterlis@yale.edu.
Jazyk: angličtina
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2024 Nov; Vol. 50 (1), pp. 153-163. Date of Electronic Publication: 2024 Jul 22.
DOI: 10.1038/s41386-024-01913-3
Abstrakt: The development of novel radiotracers for Positron Emission Tomography (PET) imaging agents targeting the synaptic vesicle glycoprotein 2 A (SV2A), an integral glycoprotein present in the membrane of all synaptic vesicles throughout the central nervous system, provides a method for the in vivo quantification of synaptic density. This is of particular interest in neuropsychiatric disorders given that synaptic alterations appear to underlie disease progression and symptom severity. In this review, we briefly describe the development of these SV2A tracers and the evaluation of quantification methods. Next, we discuss application of SV2A PET imaging to the study of depression, including a review of our findings demonstrating lower SV2A synaptic density in people with significant depressive symptoms and the use of a ketamine drug challenge to examine synaptogenesis in vivo. We then highlight the importance of performing translational PET imaging in animal models in conjunction with clinical imaging. We consider the ongoing challenges, possible solutions, and present preliminary findings from our lab demonstrating the translational benefit and potential of in vivo SV2A imaging in animal models of chronic stress. Finally, we discuss methodological improvements and future directions for SV2A imaging, potentially in conjunction with other neural markers.
(© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)
Databáze: MEDLINE
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