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bioRxiv · 10.1101/2020.04.10.035352

A High-Resolution In Vivo Atlas of the Human Brain's Benzodiazepine Binding Site of GABAA Receptors

Norgaard, M.·Beliveau, V.·Ganz, M.·Svarer, C.·Pinborg, L. H.·Keller, S. H.·Jensen, P. S.·Greve, D. N.·Knudsen, G. M.
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Abstract

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human brain and plays a key role in several brain functions and neuropsychiatric disorders such as anxiety, epilepsy, and depression. The binding of benzodiazepines to the benzodiazepine receptor sites (BZR) located on GABAA receptors (GABAARs) potentiates the inhibitory effect of GABA leading to the anxiolytic, anticonvulsant and sedative effects used for treatment of those disorders. However, the function of GABAARs and the expression of BZR protein is determined by the GABAAR subunit stoichiometry (19 genes coding for individual subunits), and it remains to be established how the pentamer composition varies between brain regions and individuals. Here, we present a quantitative high-resolution in vivo atlas of the human brain BZRs, generated on the basis of [11C]flumazenil Positron Emission Tomography (PET) data. Next, based on autoradiography data, we transform the PET-generated atlas from binding values into BZR protein density. Finally, we examine the brain regional association with mRNA expression for the 19 subunits in the GABAAR, including an estimation of the minimally required expression of mRNA levels for each subunit to translate into BZR protein. This represents the first publicly available quantitative high-resolution in vivo atlas of the spatial distribution of BZR densities in the healthy human brain. The atlas provides a unique neuroscientific tool as well as novel insights into the association between mRNA expression for individual subunits in the GABAAR and the BZR density at each location in the brain.

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Norgaard, M., Beliveau, V., Ganz, M., Svarer, C., Pinborg, L. H., Keller, S. H., Jensen, P. S., Greve, D. N., Knudsen, G. M.. 2020-04-10. A High-Resolution In Vivo Atlas of the Human Brain's Benzodiazepine Binding Site of GABAA Receptors. https://doi.org/10.1101/2020.04.10.035352

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