The effect of glial cell line‐derived neurotrophic factor (GDNF) on the growth of mesencephalic dopaminergic neurons and on their survival following exposure to the neurotoxin 1‐methyl‐4‐phenylpyridinium (MPP+) was examined in vitro. In cultures developing under normal conditions, GDNF at 1 ng/ml optimally improved the survival and stimulated the growth of dopaminergic neurons without affecting glial growth. In cultures treated with MPP+, GDNF could not prevent toxicity to dopaminergic neurons. The uptake of [3H]dopamine and the number of tyrosine hydroxylase‐positive neurons were similarly reduced by MPP+ in the presence or absence of GDNF. However, after removal of MPP+, GDNF protected dopaminergic neurons from the continuous cell death and stimulated the regrowth of dopaminergic fibers damaged by MPP+. We conclude that GDNF supports the growth of normally developing dopaminergic neurons and stimulates their survival and recovery after damage. These findings suggest that GDNF could be useful in the development of therapeutic approaches to Parkinson's disease, which is characterized by dopaminergic cell loss.
Objectives
To study the effects of levodopa and walking speed on gait variability in individuals with Parkinson's disease (PD).
Methods
Thirty-three individuals with PD were studied. Their mean age was 70.61 ± 9.23 yr. The average time since diagnosis was 9.65 ± 5.80 yr years. Gait variability was studied while “OFF” and “ON” dopaminergic medication when the subjects walked at their usual and fastest speeds.
Results
Variability of step time, double support time, stride length and stride velocity decreased significantly (p = .037; p = .037; p = .022; p = .043, respectively) after dopaminergic treatment. When subjects increased walking speed, the variability of stride length and stride velocity decreased significantly (p = .038 and p = .004, respectively) both while “OFF” and “ON” levodopa. Increasing walking speed did not change the variability of step time and double support time regardless of medication status.
Conclusions
Levodopa decreased gait variability in persons with PD. Stride length and stride velocity variability appeared to be speed dependent parameters, whereas, the variability of step time and double support time appeared to be speed independent measures. Levodopa had positive effects on gait stability in PD.
Neurotrophic factors have been shown to support the survival and promote the recovery of injured neurons both in vivo and in vitro. Here, we investigated whether glial cell line-derived neurotrophic factor (GDNF) and basic fibroblast growth factor (bFGF) could modify the damage to dopamine (DA) neurons in mesencephalic cultures caused by the neurotoxin 6-hydroxydopamine (6-OHDA). The data show that bFGF, but not GDNF, effectively protected DA neurons from 6-OHDA toxicity. Because bFGF is a glial mitogen, whereas GDNF is not, we tested whether glial cells participated in bFGF neuroprotection. Inhibition of glial cell proliferation completely prevented the protective effect of bFGF. Because oxidative events have been associated with 6-OHDA-induced damage, we examined the levels of glutathione (GSH) in control and bFGF-treated cultures. Cultures treated with bFGF had higher levels of GSH, which increased even further in response to 6-OHDA exposure. Control cultures failed to up-regulate GSH levels after 6-OHDA, suggesting a relationship between increased GSH levels and protection from 6-OHDA. Inhibition of glial cell proliferation prevented the rise in GSH in bFGF-treated cultures and abolished the increase after 6-OHDA treatment. Protection from 6-OHDA by bFGF was also diminished when GSH levels were decreased by the GSH synthesis inhibitor L-buthionine sulfoximine. Our study shows that stimulation of glial cells by bFGF allows the up-regulation of antioxidant defenses and supports cell survival during oxidative stress.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.