title: In vivo imaging of inhibitory, GABAergic neurons by MRI.
abstract: The unambiguous detection of specific neuronal subtypes is up to now only possible with invasive techniques or optical imaging after genetic modification. High field magnetic resonance imaging (MRI) has the ability to visualize the brain structure and anatomy noninvasively, with high resolution--but missing the cell specific and functional information. Here we present a new tool for neuroimaging with MRI, enabling the selective detection of GABAergic neurons under in vivo conditions. The specific imaging contrast is achieved by a novel paramagnetic contrast agent, which responds to the activity of the enzyme glutamic acid decarboxylase--expressed solely by inhibitory neurons. The relaxivity of the complex is increased upon decarboxylation of two glutamic acid moieties, thus allowing increased water access to the inner and outer coordination spheres of the paramagnetic ion. The mechanism and specificity of activation were proven with tissue lysates and further applied to a differentiation protocol for murine embryonic stem cells. The relaxation enhancement was studied quantitatively and revealed decreased longitudinal relaxation times in the inhibitory neuron samples compared to the naïve stem cells in vitro and in vivo. Furthermore, this approach offers not only the discrimination of inhibitory, GABAergic neurons in the brain but also may expand the usefulness of MRI for functional imaging on a cellular level.
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Neurological Research, Cologne, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Aswendt
authors.forename: Eliana
authors.initials: E
authors.lastname: Gianolio
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pariani
authors.forename: Roberta
authors.initials: R
authors.lastname: Napolitano
authors.forename: Franco
authors.initials: F
authors.lastname: Fedeli
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D001931:Brain Mapping / Q000379:methods*; D003287:Contrast Media / Q000737:chemistry; D059330:GABAergic Neurons / Q000166:cytology* / Q000378:metabolism; D005682:Gadolinium; D015151:Immunoblotting; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D003287:Contrast Media; D005682:Gadolinium