Challenges and Rewards of In Vivo Synaptic Density Imaging, and Its Application to the Study of Depression

Authors

Ruth H Asch
Chadi G Abdallah
Richard E Carson
Irina Esterlis

Language

English

Publication Date

11-1-2024

Journal

Neuropsychopharmacology

DOI

10.1038/s41386-024-01913-3

PMID

39039139

PMCID

PMC11525584

PubMedCentral® Posted Date

7-22-2024

PubMedCentral® Full Text Version

Post-print

Abstract

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.

Keywords

Humans, Animals, Positron-Emission Tomography, Synapses, Membrane Glycoproteins, Depression, Nerve Tissue Proteins, Brain

Comments

This article has been corrected. See Neuropsychopharmacology. 2025 Mar 19;50(6):1019.

Published Open-Access

yes

Recommended Citation

Asch, Ruth H; Abdallah, Chadi G; Carson, Richard E; et al., "Challenges and Rewards of In Vivo Synaptic Density Imaging, and Its Application to the Study of Depression" (2024). Faculty and Staff Publications. 6018.
https://digitalcommons.library.tmc.edu/baylor_docs/6018