[Growth factors as neuroprotective treatment in Parkinson disease?].
BACKGROUND
One of several probable causation theories of Parkinson disease postulates that brain tissue cannot generate sufficient levels of various growth factors required to sustain the viability of dopamine-producing nerve cells in the presence of as yet unknown toxic factors. The study reported here evaluates the ability of externally applied growth factors to protect the dopamine fibres in the basal ganglia in a toxin-induced animal model of the disease.


METHODS
All animals (rats) were subjected to selective destruction of the dopamine-producing cells in substantia nigra. The rats were divided into three groups. Two groups received intracerebral treatment with either glia-cell derived neurotrophic factor (GDNF) or a combination of brain-derived neurotrophic factor (BDNF) and GDNF. The third group acted as untreated controls and were given sterile saline. The growth factors were infused directly into the brain by an osmotic pump over a period of 28 days. Brain sections taken from all three groups were evaluated by immunocytochemistry.


RESULTS
The two groups of rats that received growth factor infusion displayed a significant improvement in their motor behaviour compared to control animals. Immunocytochemistry studies demonstrated that the group receiving a combination of GDNF and BDNF had an increased number of surviving active fibres in the dopamine system striatum in comparison to the control and GDNF groups. In addition the infusion of growth factors resulted in a proliferation of subventricular cells in the basal ganglia.


CONCLUSIONS
The improved motor function following growth factor treatment in this rat model might be due to a delayed retrograde degeneration of the nigrostriatal nerve fibers. Growth factor infusion also clearly stimulated endogenous stem cells and caused their migration towards the striatum. Our observations indicate that the infusion of growth factors into the brain have a symptomatic and neuroprotective effect in this model.
Centre for Molecular Biology and Neuroscience (CMBN), Universitetet i Oslo, Postboks 1105 Blindern, 0317 Oslo. torp@basalmed.uio.no
Reidun
R
Torp
Preet Bano
PB
Singh
Dag R
DR
Sørensen
Espen
E
Dietrichs
Henry
H
Hirschberg
D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage*; D006801:Humans; D007150:Immunohistochemistry; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D011954:Receptors, Dopamine