Releasing the brakes on spinal cord growth - the working group led by Professor Frank Bradke is studying how nerve cells can be stimulated to regenerate themselves in the case of paraplegia

Bonn, February 8^th, 2012. The new working group led by Professor Frank Bradke at the DZNE is studying how nerve cells can be stimulated to regenerate themselves in the case of paraplegia

While broken bones, muscle tears or wounds in the skin usually heal by themselves, the situation is different in the spinal cord. If the spinal cord is severed, it never grows together again. The result is paraplegia. Yet why doesn’t the spinal cord regenerate? And how can people suffering from paraplegia nevertheless be helped? These questions stand at the centre of research being conducted by Professor Frank Bradke and his new working group at the German Centre for Neurodegenerative Diseases (DZNE) in Bonn.

Nerve cells in the central nervous system are surrounded by a myelin sheath. This layer protects the nerve cells but also prevents their regeneration following injuries. It contains a whole series of molecules that may prevent the regrowth of nerve fibres. According to Bradke, these molecules are “comparable to stop signs for road traffic.” If a nerve fibre encounters such a stop sign, it does not grow any further. Scientists around the world are working to identify these growth-inhibiting molecules. Bradke has chosen a different approach, however: he and his working group are focusing on the nerve cells themselves. Why do they stop at the stop signs? Can nerve cells be made to ignore the stop signs and simply continue growing? “We are trying to turn nerve cells into somewhat more reckless drivers,” says Bradke. Bradke’s previous work has already demonstrated that this approach is highly promising: he has shown using animal models that small quantities of Taxol, a substance that is also used in cancer therapy, can stabilise the cytoskeleton of the nerve cells in such a way that severed nerve cells are stimulated to grow again.

Bradke’s discovery that Taxol could help regrow severed nerves was the result of many years of research on nerve cell development. In the early stages of development a nerve cell starts to produce a range of cellular projections. One of these projections becomes the axon and grows rapidly. Axons can be up to one metre long in the spinal cord of humans and they transmit electrical nerve signals to downstream cells. All other projections become dendrites – they are shorter and receive the signals from upstream nerve cells. During his doctoral studies Bradke was already investigating how the development of the axon differs from that of dendrites and why it is that axons continue to grow while dendrites stop growing.

Bradke demonstrated that the cytoskeleton plays a fundamental role in this respect. The growth cone at the end of the axon contains actin bundles. These must be flexible enough so that the axon can grow. The axon itself contains microtubules which give the long projections of the nerve cells their structure. In the growth cone these must be stable enough to push the actin filaments forwards. A nerve projection can only grow when the microtubules are stable enough and the actin filaments are unstable enough. This is the case in axons but not in dendrites. Following an injury to the spinal cord, microtubules in the axons are destroyed and become unstable – the axon can therefore no longer grow. Would it be possible, asked Bradke, to restore the ability of axons to grow simply by stabilising the microtubules? Taxol is a substance that stabilises microtubules. Bradke and his colleagues showed that administering small quantities of Taxol induced nerve growth. “Taxol also has another property: it prevents the formation of scars. This makes the regeneration of the nerve fibres considerably easier,” says Bradke.

These research results are still a long way from practical implementation in clinical settings, but they do give important suggestions for new directions in research. Treatments that directly affect the cytoskeleton can boost the growth of nerve cells. “In the long term our research can also contribute to a better understanding of neurodegenerative diseases of the brain such as stroke, Parkinson and Alzheimer’s Disease, because nerve cells are also damaged in these diseases and axons lose their contacts with downstream cells,” Bradke says.

Frank Bradke studied at Freie Universität Berlin and at University College London. In 1994 he received a Bachelor of Science in Anatomy and Developmental Biology and in 1995 he received his Diploma in Biochemistry. During his doctoral work he conducted research at the European Molecular Biology Laboratory (EMBL) in Heidelberg. He took up postdoctoral positions at the University of California, San Francisco, and Stanford in 2000 and then became the head of the Neurobiology Working Group at the Max Plank Institute in Martinsried. In 2009 Frank Bradke received his venia legendi from LMU Munich. Since 2011 he has been a full professor and Senior Research Group Leader of the "Axonal Growth and Regeneration Working Group" at DZNE in Bonn.

The homepage of the workgroup is found here.

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