caa a22 4500 606203044 CHVBK 20210128100955.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00429-014-0801-1 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0801-1 Molecular imaging reveals epileptogenic Ca2+-channel promoter activation in hippocampi of living mice [Elektronische Daten] [Rebecca Kulbida, Yipeng Wang, Eva-Maria Mandelkow, Susanne Schoch, Albert Becker, Karen van Loo] Focal epilepsies often originate in the hippocampal formation of the temporal lobe (temporal lobe epilepsy) and are generally acquired after transient brain insults. Such insults induce cellular and structural reorganization processes of the hippocampus, referred to as epileptogenesis that finally convert the brain spontaneous epileptic. Here, we developed a new molecular imaging strategy in a state-of-the-art animal model to provide insights into key epileptogenic mechanisms. Our new approach combines recombinant adeno-associated virus (rAAV) gene delivery with in vivo bioluminescence imaging. rAAV particles harboring the luciferase reporter gene under control of the minimal T type Ca2+-channel subunit Ca V 3.2-promoter were generated and injected stereotaxically in the hippocampal region of mice. Bioluminescent signals, corresponding to Ca V 3.2 promoter activation, were imaged in vivo in the pilocarpine model of status epilepticus (SE). We detected activation of key Ca V 3.2 promoter motifs at 3 and 10days after SE but not after the onset of chronic seizures. These data suggest Ca V 3.2 promoter activation as novel anti-epileptogenic target. In more general terms, we have established an experimental approach that allows to follow cerebral gene promoter dynamics longitudinally and to correlate this activity to behavioral parameters in the same mice. Springer-Verlag Berlin Heidelberg, 2014 Molecular neuroimaging nationallicence Epilepsy nationallicence Pilocarpine animal model nationallicence Transcriptional channelopathies nationallicence T type calcium channel CaV3.2 nationallicence In vivo bioluminescence imaging nationallicence Kulbida Rebecca Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53105, Bonn, Germany aut Wang Yipeng DZNE, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175, Bonn, Germany aut Mandelkow Eva-Maria DZNE, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175, Bonn, Germany aut Schoch Susanne Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53105, Bonn, Germany aut Becker Albert Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53105, Bonn, Germany aut van Loo Karen Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53105, Bonn, Germany aut Brain Structure and Function Springer Berlin Heidelberg 220/5(2015-09-01), 3067-3073 1863-2653 220:5<3067 2015 220 429 https://doi.org/10.1007/s00429-014-0801-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 brief-communication jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0801-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kulbida Rebecca Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53105, Bonn, Germany aut NATIONALLICENCE 700 1- Wang Yipeng DZNE, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175, Bonn, Germany aut NATIONALLICENCE 700 1- Mandelkow Eva-Maria DZNE, German Center for Neurodegenerative Diseases, Ludwig-Erhard-Allee 2, 53175, Bonn, Germany aut NATIONALLICENCE 700 1- Schoch Susanne Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53105, Bonn, Germany aut NATIONALLICENCE 700 1- Becker Albert Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53105, Bonn, Germany aut NATIONALLICENCE 700 1- van Loo Karen Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53105, Bonn, Germany aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/5(2015-09-01), 3067-3073 1863-2653 220:5<3067 2015 220 429