Department of Neuropathology
University of Bonn, Medical Center
D- 53127 Bonn
Phone +49 (0) 228 287-19346
Fax +49 (0) 228 287-19362
Curriculum vitae Dr. Karen van Loo
Temporal lobe epilepsy (TLE) is a common and severe, often therapy-refractory seizure disorder. Previously, we have observed a striking, new mode of neuronal plasticity critical for the development of chronic recurrent seizures after status epilepticus (SE). We found that SE induced by administration of the convulsant pilocarpine causes a transformation of most CA1 pyramidal cells from regular- to burst-firing mode, which profoundly modifies the input-output properties of a subset of CA1 neurons. By complementary electrophysiological, pharmacological and molecular approaches we observed the underlying mechanism to be the specific transcriptional upregulation of Cav3.2, a T-type Ca2+ channel subunit. Our major goal is to understand the role of these neurons in generating seizure activity in hippocampal micronetworks and subsequently to antagonize the epileptogenesis, which can be used to develop new strategies for pharmacological intervention in TLE pathogenesis, including the design of gene/pathway-specific drugs.
We perform state-of-the-art molecular, cellular, neuropathological and telemetric EEG-/video monitoring experiments, including the use of adeno-associated viral (AAV) approaches, in vivo bioluminescence imaging and transgenic mouse models.
5 most important publications
1. Ekstein D, Benninger F, Daninos M, Pitsch J, Van Loo KM, Becker AJ, Yaari Y. (2012) Zinc Induces Long-Term Upregulation of T-Type Calcium Current in Hippocampal Neurons in Vivo. J Physiol, 590(22): 5895-905.
2. Van Loo KM, Schaub C, Pernhorst K, Yaari Y, Beck H, Schoch S, Becker AJ. (2012) Transcriptional
regulation of T-type calcium channel CaV3.2: bi-directionality by early growth response 1 (Egr1) and repressor element 1 (RE-1) protein-silencing transcription factor (REST). J Biol Chem, 287: 15489-15501.
3. Verheij MM, De Mulder EL, De Leonibus E, Van Loo KM, Cools AR (2008) Rats that differentially respond to cocaine differ in their dopaminergic storage capacity of the nucleus accumbens. J Neurochem, 105(6): 2122-2133.
4. van Loo KM, Martens GJ. (2007) Identification of genetic and epigenetic variations in a rat model for
neurodevelopmental disorders. Behav Genet, 37(5): 697-705.
5. Coolen MW, Van Loo KM, Van Bakel NN, Pulford DJ, Serneels L, De Strooper B, Ellenbroek BA, Cools AR, Martens GJ. (2005) Gene dosage effect on gamma-secretase component Aph-1b in a rat model for neurodevelopmental disorders. Neuron, 45: 497-503.