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

Yeona Kang1,2, Sandra Milena Hurtado Rúa3, Ulrike W Kaunzner4

  • 1Department of Radiology, Weill Cornell Medicine, New York, NY, 10021, USA.

Molecular Imaging and Biology
|May 13, 2020
PubMed
Summary

Multiple sclerosis patients show higher gamma-aminobutyric acid (GABA) A receptor binding, linked to increased immune activity. This suggests immune-driven GABAergic abnormalities may play a role in MS pathogenesis.

Keywords:
FlumazenilGABAA receptor bindingMultiple sclerosisNeuroinflammationPK11195Positron emission tomography

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Area of Science:

  • Neuroscience
  • Immunology
  • Radiology

Background:

  • Gamma-aminobutyric acid (GABA) is a key inhibitory neurotransmitter crucial for brain function.
  • The GABAergic system exhibits immunomodulatory effects and can adapt to excitotoxicity.
  • The relationship between the GABAergic system and inflammation in multiple sclerosis (MS) is not well understood.

Purpose of the Study:

  • To investigate the in vivo relationship between GABA A receptor binding and the innate immune response in MS patients.
  • To explore potential immune-driven GABAergic abnormalities in multiple sclerosis.

Main Methods:

  • Positron emission tomography (PET) imaging was used with [11C] flumazenil (FMZ) to assess GABA A receptor binding and [11C]-PK11195 (PK-PET) to measure activated microglia/macrophages.
  • Dynamic FMZ-PET and PK-PET imaging were performed on 16 MS patients and single FMZ-PET on 10 healthy controls (HC).
  • GABA A receptor binding and PK-PET distribution volume ratios were calculated, and their association was analyzed using a hierarchical linear model.

Main Results:

  • MS patients exhibited significantly higher GABA A receptor binding in the cortex compared to HC (p=0.002).
  • A significant positive correlation was observed between FMZ binding and PK-PET within the cortex (r=0.61, p<0.001).
  • Correlations were also significant in the occipital, parietal, and cingulate regions.

Conclusions:

  • Multiple sclerosis patients demonstrate higher GABA A receptor density compared to healthy controls.
  • This increased receptor density is correlated with heightened innate immune activity.
  • The findings suggest that immune-driven GABAergic abnormalities may be present in multiple sclerosis.