Prof. Dr. med. Thomas J. Feuerstein
Every year, approximately 50 Fellows are invited to work on their projects at FRIAS for 2 to 12 months in an intellectually stimulating environment. Fellows that have already been at FRIAS before can return to FRIAS for 2 to 6 weeks within the framework of the Alumni Programme, for example in order to finish a project. Furthermore, junior and senior researchers are regularly invited as guest researchers.
Our Research Focus profited enormously from the international team of Fellows and guest researchers at FRIAS.
Prof. Dr. Tobias Schätz, ERC Consolidator Grant 2015, Research Focus Quantum Transport 2014/15
My studies of medicine at the University of Freiburg, Germany, concluded with a dissertation at the Institute of Medical Statistics and Documentation (Topic: Simulation studies of the genetic correlation coefficient). After my - then mandatory - military service as staff physician I continued my postdoctoral work at the State Psychiatric Hospital Reichenau and the Neurological University Hospital Freiburg. Due to my strong interest in neuro- and psychopharmacology, I transferred to the Institute of Pharmacology at the University of Freiburg and specialized first in pharmacology and toxicology.
I then returned to the Neurological University Hospital to complete my training as a neurologist and qualified for my state doctorate (Habilitation) in 1988. I was awarded the Constance Medical Sponsorship in 1989.
From 1989 to 1994, I worked as Head of Department, Clinical Research CNS, at the pharmaceutical firm of Goedecke AG / Parke-Davis (Freiburg and Ann Arbor, Michigan).
In 1994, I accepted the offer to became University Professor and was appointed head of the Section of Clinical Neuropharmacology, Neurocenter of the University Hospital Freiburg.
In 1995, I ranked third for the position of Chair Pharmacology, University of Dresden. In 1996 I ranked second for the same position at the University of Göttingen and, after the lead candidate declined, was given the first position.
My current research interests are focused on a focal neocortical epilepsy model in the rat to test local anti-epileptic therapies and transporter-mediated selective GABA release as an endogenous anti-seizure mechanism.
- Feuerstein TJ, Limberger N (1999) Mathematical analysis of the control of neurotransmitter release by presynaptic receptors as a supplement to experimental data. Naunyn-Schmiedeberg´s Arch Pharmacol 359:349-359
- Stefan H, Feuerstein TJ (2007) Novel anticonvulsant drugs. Pharmacol Ther 113:165-183
- Feuerstein TJ (2008) Presynaptic receptors for dopamine, histamine and serotonin.Handb Exp Pharmacol 184:289-338
- Feuerstein TJ, Kammerer M, Lücking CH, Moser A (2011) Selective GABA release as a mechanistic basis of high frequency stimulation used for the treatment of neuropsychiatric diseases. Naunyn-Schmiedberg´s Arch Pharmacol 384:1-20
- Rassner MP, van Velthoven-Wurster V, Ramantani G, Feuerstein TJ (2013) Altered transporter-mediated neocortical GABA release in Rasmussen encephalitis. Epilepsia 54(3):e41–e44
Transporter-mediated GABA release as endogenous anti-seizure defense mechanism
The human brain is predisposed to epileptic seizures under certain circumstances. Fortunately, endogenous anti-seizure mechanisms usually prevent such seizures. One of the most important mechanisms in this regard is transporter-mediated GABA release. The notion that synaptic transmission occurs solely by exocytosis is definitely not the case for GABA neurons. Transporter-mediated GABA release happens, for instance, when neurons are robustly depolarized due to repetitive influx of Na+ as occurs during epileptic seizures.
We characterized veratridine-evoked 3H-GABA release from human neocortical synaptosomes as caused solely by transporter reversal due to both depolarization and increased cytosolic Na+ ([Na+]i). Surprisingly, removal of extracellular Ca2+ ([Ca2+]e) increased this release, most probably by activating the synaptosomal Na+/Ca2+ exchanger (NCX) which further elevated [Na+]i and thus enhanced veratridine-induced transporter reversal. Increased GABA release due to decreased [Ca2+]e may counteract paroxysmal activity as lowering [Ca2+]e can induce spreading epileptiform activity.
My FRIAS project will investigate this anti-seizure defense mechanism in synaptosomes and in slices of human and rat neocortex. Methods are synaptosomal GABA release and patch-clamp analysis of pyramidal cells and GABAergic interneurons. The pre- and postsynaptic NCX will be analyzed at different [Ca2+]e to determine whether NCX modulation provides an antiepileptic target of possible clinical relevance. Specifically, a NCX-activating drug may offer a new anticonvulsant mechanism having a favorable side effect profile; i.e., this drug would selectively enhance (quasi-physiologically) an endogenous antiepileptic process, even more so when applied locally to ameliorate a seizure focus, yet not alter peripheral processes (e.g., cardiovascular).