Protecting the neuronal architecture
Researchers investigate new approaches to treating neurodegenerative
diseases

Date:
June 5, 2020
Source:
University of Heidelberg
Summary:
Protecting nerve cells from losing their characteristic
extensions, the dendrites, can reduce brain damage after a
stroke. Neurobiologists have demonstrated this by means of research
on a mouse model.



FULL STORY ========================================================================== Protecting nerve cells from losing their characteristic extensions, the dendrites, can reduce brain damage after a stroke. Neurobiologists from Heidelberg University have demonstrated this by means of research on a
mouse model. The team, led by Prof. Dr Hilmar Bading in cooperation with
Junior Professor Dr Daniela Mauceri, is investigating the protection
of neuronal architecture to develop new approaches to treating neurodegenerative diseases.

The current research findings were published in the journal "Proceedings
of the National Academy of Sciences."

========================================================================== Brain nerve cells possess many arborised dendrites, which can make
connections with other neurons. The highly complex, ramified structure
of neurons is an important precondition for their ability to connect with
other nerve cells, in order to enable the brain to function normally. In earlier studies, the Heidelberg researchers identified the signal molecule VEGFD -- Vascular Endothelial Growth Factor D -- as a central regulator
for maintaining and restoring neuronal structures. "Our current research results demonstrate that a stroke as a consequence of an interruption of
the blood supply to the brain leads to a reduction of VEGFD levels. That
causes the nerve cells to lose part of their dendrites. They shrink
and this leads to impairments of the cognitive and motor abilities,"
explains Prof. Bading.

Based on these findings, the researchers at the Interdisciplinary
Centre for Neurosciences explored the question of whether the reduction
of neuronal structures after a stroke can be prevented by restoring the
VEGFD levels. To that effect, they applied recombinant VEGFD -- produced
using biotechnological methods -- to the brains of mice that had suffered
a stroke. "The treatment successfully preserved the dendritic arborisation
and, what is important, brain damage was reduced. Furthermore, the motor abilities recovered more quickly," says Prof. Mauceri. In a second step,
the researchers administered a modified form of VEGFD as nose drops,
in order to simplify the treatment. They achieved the same results with
this peptide mimetic, i.e. a simplified but biologically still effective version of VEGFD, which was developed in cooperation with Prof.

Dr Christian Klein from Heidelberg University's Institute of Pharmacy
and Molecular Biotechnology.

The scientists hope that their research findings to protect the neuronal architecture will lead to new approaches to treating stroke in the
long run.

"The principle of nasal delivery, in particular, would be a safe and
simple form of intervention," says Prof. Bading. The Heidelberg scientists
are now working on expanding the treatment trialled in the mouse model
with a view to a possible clinical application.

The research work was funded by the German Research Foundation and the
European Research Council.


========================================================================== Story Source: Materials provided by University_of_Heidelberg. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Daniela Mauceri, Bettina Buchthal, Thekla J. Hemstedt, Ursula Weiss,
Christian D. Klein, Hilmar Bading. Nasally delivered VEGFD mimetics
mitigate stroke-induced dendrite loss and brain damage. Proceedings
of the National Academy of Sciences, 2020; 117 (15): 8616 DOI:
10.1073/ pnas.2001563117 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200605121527.htm

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