Article
Gabapentin-lactam as a neuroprotective agent on E14 rat ventral mesencephalon dissociated embryonic cell cultures
Gabapentin-lactam ist ein neuroprotektiver Wirkstoff für dopaminerge Neurone in Zellkulturen des embryonalen Mescencephalins
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Published: | April 23, 2004 |
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Outline
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Objective
Parkinson's disease (PD) is one of the most common neurodegenerative diseases. During the early onset in the disease, dopamine (DA)-containing neurons in the substantia nigra pars compacta (SNc) degenerate, leading to slower movements, rigidity, resting tremor and postural imbalance. In contrast to other neurodegenerative disorders, a relatively good symptomatic therapy for PD does exist consisting mainly of dopamine replacement and adjuvant surgical therapy that relieves most motor symptoms. However, there is still a need for a novel therapy preventing cell death ('neuroprotective') or restoring degenerating neurons in PD ('neurorestorative'). In this study, a potential neuroprotective agent gabapentin-lactam (GBP-L) is evaluated in vitro.
Methods
In order to test the effect of GBP-L on primary cultures of dopaminergic (DAergic) neurons, the ventral mesencephalon of E14 Spargue Dawley rat embryos was removed and dissociated. Cells were plated at a concentration of 100,000 cells/cm2 in 48-well plates precoated with 0.01% poly-L-ornithine. At 4 days in vitro, cultures were treated for 24h with 10µM, 15µM or 30µM concentrations of hydroxydopamine (6-OHDA) in the absence or presence of 500µM, 250µM, 100µM or 50µM GBP-L. Quantitative and morphometric analysis were focussed on cell cultures stained for tyrosine hydroxylase (TH), DAPI and β-tubulin (Tub-1).
Results
6-OHDA treatment resulted in a dose-depended decrease of TH+ neurons from 1.7% at 10µM, 0.9% at 15µM and 0.2% at 30µM (p<0.05% for the two latter). 500mµM GBL-P treatment resulted in a significant and complete protection at 30µM 6-OHDA induced toxicity (p<0.05). Similar results are obtained with GBP-L pre-treatment at 500µM (p<0.05%) and 250µM (p<0.05%) GBP-L concentrations but not at 100µM GBP-L.
Conclusions
To conclude, our results showed that GBP-L can protect dopamine neurons in vitro after neurotoxin treatment with 6-OHDA. These data indicate that GBP-L has neuroprotective potentials with possible clinical implications. Further studies will be interesting to evaluate the neuroprotective mechanism of GBP-L and its in vivo potentials.