Dopamine neurons have an important role in cognitive control,
learning and motor control. Glial cell line-derived neurotrophic factor (GDNF) is best known for its ability to
protect dopaminergic neurons from damage, which is why it is currently
in clinical trials for treatment of Parkinson's patients. Nevertheless,
the significance of endogenous GDNF that is produced in our brains for
the regulation of the dopamine systems is still poorly understood.
New research results are expanding our understanding of the
physiological role of the GDNF in the function of the brain's dopamine systems. In an article
recently published in the Journal of Neuroscience
of Helsinki researchers establish that GDNF is an important
physiological regulator of the functioning of the brain's dopamine
‘The glial cell line-derived neurotrophic factor (GDNF) is an important physiological regulator of the functioning of the brain's dopamine neurons.’
Dr Jaan-Olle Andressoo from the Institute of Biotechnology has
developed new transgenic mice which have allowed researchers to gain
much more reliable information on the physiological functions of GDNF.
The studies were conducted in close cooperation with the research groups
led by Professor Mart Saarma and Dr Petteri Piepponen, docent of
The new research results indicate that the GDNF produced in the
brain regulates dopamine reuptake. Mice with no GDNF in their brains
displayed significantly stronger reuptake of dopamine into nerve
- The reuptake of dopamine is the most important factor regulating
the brain's dopamine balance and signalling. In practice this means that
differences in GDNF levels might explain certain differences in
people's ability to learn or focus, explains Jaakko Kopra, a researcher
in Andressoo's group.
In addition, the transgenic mice had an atypically low reaction to
amphetamine, which specifically targets the dopamine transporter in the
brain. These observations were associated with changes in the
functionality, amount and localization of the dopamine transporter in
the nerve endings.
So we know that GDNF regulates the amount and localization of the
dopamine transporter in the neurons, but we suspect that there may be
additional mechanisms. It seems that the relationship between GDNF and
dopamine transporter is surprisingly complex, which is of course
interesting from a researcher viewpoint, explains Kopra.
Mice with GDNF removed from their brain in adulthood displayed very
similar changes. This indicates that the underlying cause for the
changes is not the impact of GDNF on brain development. The group's
previously published studies on the same mouse models demonstrated that
contrary to expectations, the removal of GDNF does not lead to the
destruction of dopamine neurons. This means that these new results
significantly expand our understanding of physiological GDNF, from a
factor protecting dopamine neurons to a dynamic regulator of their
This knowledge is crucial for developing new treatments for not just
Parkinson's disease, but also for addiction, ADHD and bipolar disorder,
as all of these diseases are associated with some type of disorder in
the function of the dopamine neurons, and specifically in the dopamine
transporter, states Kopra.