Project: Role of FGF-2 for the amyotrophic lateral sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective motor neuron loss. The cause for the selective death is still unclear, but many different pathomechanisms are discussed including loss of neurotrophic factors. One of these factors that could play a prominent role in the motor system is basic fibroblast growth factor (FGF-2). In order to evaluate the physiological role of FGF-2 in the ALS scenario, we established double mouse mutants transgenic for the human SOD1 mutation and lacking the endogenous FGF-2 gene. The ALS-mouse model overexpressing the mutant human SOD1 is similar to the human ALS disease. Evaluation parameters of FGF-2 deficient mutant SOD1 mice include lifespan and course of disease by testing motor performance. The motor neuron number and the density of neuromuscular end plate are under investigation. These results could be important to understand the underlying pathomechanisms of ALS and help to develop new therapeutic strategies for patients with motoneuron disease.


Project: Relevance of FGF-2 in peripheral nerve regeneration

Neurotrophic factors have been shown to support peripheral nerve repair. One of the relevant factors is basic fibroblast growth factor (FGF-2), which is expressed in motor and sensory neurons as well as Schwann cells. Previous studies of the institute demonstrated that FGF-2 is up-regulated after lesion and influences early peripheral nerve regeneration by regulating Schwann cell proliferation. Evidence of the importance of FGF-2 in remyelination of peripheral nerves came from mice with FGF-2 deficiency and mice over-expressing FGF-2. By using morphometric analyses of myelinated regenerated axons and biochemical methods (quantitative RT-PCR, Western blot), we could show earlier maturation and remyelination of regenerated axons in the absence of FGF-2. Consequently, the recovery of mechanosensory but not motor function was faster in FGF-2 deficient mice. How FGF-2 selectively affects functional properties of mechanoreceptors after peripheral nerve lesion remains an open question.