2005 - Amantadine and memantine induce the expression of the glial cell line-derived neurotrophic factor in C6 glioma cells.
Caumont AS, Octave JN, Hermans E.
Laboratoire de Pharmacologie Experimentale (FARL), Universite catholique de Louvain, Avenue Hippocrate 54.10, 1200 Bruxelles, Belgium.
Aminoadamantanes are commonly used in the treatment of Parkinson's and Alzheimer's diseases. While these drugs are shown to antagonise ionotropic glutamate receptors on neuronal cells, additional mechanisms could contribute to their neuroprotective properties.
The aim of the present study was to investigate the effect of aminoadamantanes on the production of the glial cell line-derived neurotrophic factor (GDNF) in glial cells.
For this purpose, we measured the modulation of GDNF release in C6 glioma cell cultures treated for 24h with amantadine and memantine. Both drugs dose-dependently increased GDNF level in the culture medium with similar potency (submicromolar range) and efficacy (three to four-fold induction).
RT-PCR studies revealed that both compounds also increased GDNF mRNA levels and their influence on the GDNF gene transcription was further evidenced using a rat GDNF promoter luciferase reporter assay.
Together, these results demonstrate that the neuroprotective effect of amantadine and memantine could involve the regulation of GDNF production by glial cells.
PMID: 16298481 [PubMed - as supplied by publisher]
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Title
GDNF modulates HO-1 expression in substantia nigra postnatal cell cultures
SNIP
Because exogenously applied GDNF prevented HO-1 up-regulation in cultures treated with H(2)O(2) or l-DOPA, and antibody neutralization of GDNF prevented the secondary HO-1 down-regulation observed in neuron-glia cultures, we propose that GDNF negatively modulates HO-1 expression induced by oxidative stress. To our knowledge, this is the first report showing the modulation of HO-1 expression by GDNF.
ncbi.nlm.nih.gov
Title
[Cell therapy and other neuroregenerative strategies in Parkinson's disease (I).]
SNIP
OBJECTIVE. To review, from a mainly clinical standpoint, the different strategies applied to regenerate or restore the nigrostriatal dopaminergic system in Parkinson's disease. This first part focuses on the results of adrenal medulla and human fetal mesencephalic transplants, and a second part will address transplants of other cell types, administration of trophic factors, and gene therapy. DEVELOPMENT. Adrenal medulla transplants were abandoned because of their inconsistent results and high morbidity. Although fetal mesencephalic transplantation can produce long-term restoration of striatal dopamine deficiency, this neurochemical effect is clinically inadequate in presence of progressive neuronal loss. Other strategies with similar 'dopaminergic' action mechanism are not a therapeutic option in this setting. CONCLUSIONS. The objective of neuroregenerative therapy for Parkinson's disease should include trophic restoration of damaged neuronal systems, since improvement in striatal dopaminergic function is not sufficient. After the recent failure of the direct (intraventricular or intraputaminal) administration of glial cell line-derived neurotrophic factor (GDNF), attention of researchers has focused on indirect methods, including transplantation of GDNF-producing cells (carotid body cell aggregates or different genetically modified cells, including stem cells), and in vivo gene therapy.
ncbi.nlm.nih.gov
Title
Transplantation of glial cell line-derived neurotrophic factor-expressing cells into the striatum and nucleus accumbens attenuates acquisition of cocaine self-administration in rats.
SNIP
Moreover, rats that received a chronic infusion of GDNF via a micro-osmotic pump also exhibited weak cocaine self-administration. Therefore, we conclude that exogenous augmentation of GDNF repositories may be useful in suppressing cocaine self-administration.
ncbi.nlm.nih.gov
Title
Expression of GDNF and GDNFR-alpha mRNAs in muscles of patients with motor neuron diseases.
SNIP
The mRNA expression levels of GDNF, GDNFR-alpha and RET were examined in the muscles of amyotrophic lateral screlosis (ALS) and X-linked spinal and bulbar muscular atrophy (SBMA).
GDNF mRNA levels were significantly elevated to variable extent in the diseased muscles compared to control muscles, although they were not specific to the type of the diseases.
The diseased muscles also have a different expression pattern of GDNF mRNA isoforms from controls.
GDNF mRNA expression, however, tended to reduce in advanced muscle pathology.
On the other hand, GDNFR-alpha mRNA levels were not changed significantly on expression levels in the diseased muscles.
In situ hybridization study revealed that GDNF and GDNFR-alpha mRNAs were localized in subsarcolemmal space of muscle cells.
RET mRNA was not detected in control nor diseased muscles.
These results suggest that the elevated muscle GDNF acts as a trophic signal for motor neurons of motor neuron diseases, implying a possible therapeutic implication of GDNF to this type of diseases.
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