The focus of Dirk Isbrandt’s research is on the investigation of molecular mechanisms underlying disease-associated changes in cellular excitability using transgenic mouse models. His team specifically investigates the impact of disease-associated mutations on neuronal ion channels, which cause the so-called ion channel diseases („channelopathies“). His research involves the identification and functional characterization of mutations in ion channel genes and the generation of corresponding mouse models. Using these transgenic mice, he studies the consequences of reversible functional inactivation or chronic loss of neuronal ion channels by employing a multidimensional strategy that is designed to correlate changes in hippocampal, cortical, and basal ganglia network activities, as well as synaptic plasticity with behavioral responses and cognitive functions. In addition, his research is aimed at testing pharmacological treatments to prevent, attenuate, or normalize the observed changes in network activity and cognitive performance.
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- Generation and characterization of transgenic mouse models using:
- acute and chronic multi-channel depth recordings from neonatal and adult mice
- chronic video EEG telemetry
- behavioral analyses including characterization of motor behavior and cognitive performance
- molecular biological characterization including single-cell RNA-Seq
- analysis of brain structure using immunohistochemistry and immunofluorescence microscopy and stereology
5 selected publications
1. Schlusche AK, Vay SU, Kleinenkuhnen N, Sandke S, Campos-Martín R, Florio M, Huttner W, Tresch A, Roeper J, Rueger MA, Jakovcevski I, Stockebrand M, Isbrandt D (2021) Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice. Proceedings of the National Academy of Sciences of the United States of America, 118(35)https://doi.org/10.1073/pnas.2009393118
2. Marguet SL, Le-Schulte VTQ, Merseburg A, Neu A, Eichler R, Jakovcevski I, Ivanov A, Hanganu-Opatz IL, Bernard C, Morellini F, Isbrandt D (2015) Treatment during a vulnerable developmental period rescues a genetic epilepsy. Nature Medicine, 21(12):1436–1444. https://doi.org/10.1038/nm.3987
3. Peters HC, Hu H, Pongs O, Storm JF, Isbrandt D (2005) Conditional transgenic suppression of M channels in mouse brain reveals functions in neuronal excitability, resonance and behavior. Nature Neuroscience, 8(1):51–60. https://doi.org/10.1038/nn1375
4. Meier K, Merseburg A, Isbrandt D, Marguet SL, Morellini F (2020) Dentate gyrus sharp waves, a local field potential correlate of learning in the dentate gyrus of mice. The Journal of Neuroscience, 40(37):7105–7118. https://doi.org/10.1523/JNEUROSCI.2275-19.2020
5. Choe C, Atzler D, Wild PS, Carter AM, Böger RH, Ojeda F, Simova O, Stockebrand M, Lackner K, Nabuurs C, Marescau B, Streichert T, Müller C, Lüneburg N, De Deyn PP, Benndorf RA, Baldus S, Gerloff C, Blankenberg S, Heerschap A, Grant PJ, Magnus T, Zeller T, Isbrandt D, Schwedhelm E (2013) Homoarginine levels are regulated by L-arginine:glycine amidinotransferase and affect stroke outcome: results from human and murine studies. Circulation, 128(13):1451 – 461. https://doi.org/10.1161/CIRCULATIONAHA.112.000580