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Stadt Ulm, Deutschland

Spokesperson

Prof. Dr. Karin Scharffetter-Kochanek
Klinik für Dermatologie und Allergologie
Albert-Einstein-Allee 23
89081 Ulm


Head

Prof. Dr. Hartmut Geiger
Klinik für Dermatologie und Allergologie
Universität Ulm
James Franck-Ring 11c
89081 Ulm


Project 5

Relevance of FOXO3 for neuronal development, aging and degeneration

FoxO3 is a transcription factor which is activated by oxidative stress or starvation and inactivated by growth factor signalling. In the previous funding period, we generated transgenic mice that conditionally express constitutively activated as well as dominant negative FoxO3 alleles. We observed an approximately 30% reduction of brain size in mice harboring the constitutively activated FoxO3 allele under control of the brain-specific CaMKII promoter. Loss of neuronal progenitor cell populations from ventricular and subventricular regions was the cause of this phenotype. Experiments designed to evaluate behavior and learning efficiency demonstrated neuromuscular hyperactivity as well as selective loss of long-term memory.

In the next funding period, we will complete the characterization of the phenotype described above. Additionally, we will investigate how postnatal induction of the constitutively activated FoxO3 transgene effects adult neurogenesis, neuronal survival and neuronal plasticity as well as longevity. We will use our established model to address the following questions: How is adult neurogenesis influenced by postnatal constitutive activation of FoxO3? How does FoxO3 influence metabolic control in neurons? Does constitutively active FoxO3 provide adult neurons a unique protection from oxidative stress? Is there a modification in neuronal lifespan?

Chief Investigator

Prof. Dr. Thomas Wirth
Director
Institute of Physiological Chemistry
Ulm University
Life Science Building, N27
James-Franck-Ring
89081 Ulm
Germany

Phone: +49 (0) 731 5002 3270
Phone: +49 (0) 731 5002 3271
Fax: +49 (0) 731 5002 2892
thomas.wirth[at]uni-ulm.de

References

List of publications from:
Thomas Wirth
>> Pubmed


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