A Multi-Ligand Imaging Study Exploring GABAergic Receptor Expression and Inflammation in Multiple Sclerosis.

TitleA Multi-Ligand Imaging Study Exploring GABAergic Receptor Expression and Inflammation in Multiple Sclerosis.
Publication TypeJournal Article
Year of Publication2020
AuthorsKang Y, Rúa SMilena Hur, Kaunzner UW, Perumal J, Nealon N, Qu W, Kothari PJ, Vartanian T, Kuceyeski A, Gauthier SA
JournalMol Imaging Biol
Volume22
Issue6
Pagination1600-1608
Date Published2020 12
ISSN1860-2002
KeywordsAdult, Case-Control Studies, Cohort Studies, Female, Flumazenil, Gray Matter, Humans, Immunity, Innate, Inflammation, Ligands, Male, Middle Aged, Multiple Sclerosis, Positron-Emission Tomography, Receptors, GABA
Abstract

PURPOSE: The γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter and essential for normal brain function. The GABAergic system has been shown to have immunomodulatory effects and respond adaptively to excitatory toxicity. The association of the GABAergic system and inflammation in patients with multiple sclerosis (MS) remains unknown. In this pilot study, the in vivo relationship between GABA binding and the innate immune response is explored using positron emission tomography (PET) with [C] flumazenil (FMZ) and [C]-PK11195 PET (PK-PET), a measure of activated microglia/macrophages.

PROCEDURES: Sixteen MS patients had dynamic FMZ-PET and PK-PET imaging. Ten age-matched healthy controls (HC) had a single FMZ-PET. GABA receptor binding was calculated using Logan reference model with the pons as reference. Distribution of volume ratio (VTr) for PK-PET was calculated using image-derived input function. A hierarchical linear model was fitted to assess the linear association between PK-PET and FMZ-PET among six cortical regions of interest.

RESULTS: GABA receptor binding was higher throughout the cortex in MS patients (5.72 ± 0.91) as compared with HC (4.70 ± 0.41) (p = 0.002). A significant correlation was found between FMZ binding and PK-PET within the cortex (r = 0.61, p < 0.001) and among the occipital (r = 0.61, p = 0.012), parietal (r = 0.49, p = 0.041), and cingulate (r = 0.32, p = 0.006) regions.

CONCLUSIONS: A higher GABA receptor density in MS subjects compared with HC was observed and correlated with innate immune activity. Our observations demonstrate that immune-driven GABAergic abnormalities may be present in MS.

DOI10.1007/s11307-020-01501-z
Alternate JournalMol Imaging Biol
PubMed ID32394283
PubMed Central IDPMC8769531
Grant ListTL1 TR000456 / TR / NCATS NIH HHS / United States
UL1 TR002384 / TR / NCATS NIH HHS / United States
Related Institute: 
Brain Health Imaging Institute (BHII)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065