Characterization of L-DOPA transport in cultured rat and mouse astrocytes

Tsai, Ming-Tzu; Lee, Eminy H.Y.

doi:10.1002/(sici)1097-4547(19960215)43:4<490::aid-jnr10>3.0.co;2-6

Cited by 45 publications

(7 citation statements)

References 28 publications

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“…On the other hand, the activation of astroglia is also closely associated with the occurrence of LID. First, astroglia are well-known to uptake and release L-DOPA (47,48), and convert L-DOPA into DA (49), indicating that astroglia might be an important source of exogenous DA in the striatum. Second, monoamine oxidase in astroglia metabolizes DA, to produce toxic reactive oxygen species and DA metabolites (50).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Alleviates Levodopa-Induced Dyskinesia in Rats

Zheng

Fan

et al. 2021

Front. Immunol.

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Dyskinesia is a serious complication of Parkinson’s disease during levodopa (L-DOPA) treatment. The pathophysiology of L-DOPA-induced dyskinesia (LID) is complex and not fully illuminated. At present, treatment of dyskinesia is quite limited. Recent studies demonstrated neuroinflammation plays an important role in development of LID. Thus, inhibition of neuroinflammation might open a new avenue for LID treatment. Resveratrol (RES) is the most well-known polyphenolic stilbenoid and verified to possess a large variety of biological activities. DA neurotoxicity was assessed via behavior test and DA neuronal quantification. The movement disorders of dyskinesia were detected by the abnormal involuntary movements scores analysis. Effects of RES on glial cells-elicited neuroinflammation were also explored. Data showed that RES attenuated dyskinesia induced by L-DOPA without affecting L-DOPA’s anti-parkinsonian effects. Furthermore, RES generated neuroprotection against long term treatment of L-DOPA-induced DA neuronal damage. Meanwhile, RES reduced protein expression of dyskinesia molecular markers, ΔFOS B and ERK, in the striatum. Also, there was a strong negative correlation between DA system damage and ΔFOS B level in the striatum. In addition, RES inhibited microglia and astroglia activation in substantia nigra and subsequent inflammatory responses in the striatum during L-DOPA treatment. RES alleviates dyskinesia induced by L-DOPA and these beneficial effects are closely associated with protection against DA neuronal damage and inhibition of glial cells-mediated neuroinflammatory reactions.

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Section: Discussionmentioning

confidence: 99%

Resveratrol Alleviates Levodopa-Induced Dyskinesia in Rats

Zheng

Fan

et al. 2021

Front. Immunol.

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“…Our data show that treatment with L-dopa for four weeks ameliorates both 6-OHDA-induced decrease of 5-HT 2B receptor expression in the brain in vivo and 6-OHDA-induced depressive behavior, suggesting the link between 5-HT 2B receptors and 6-OHDA-induced depression. Astrocytes express neutral amino acid transporter (LAT/SLC7A5) and dopamine transporter (DAT/SLC6A3) [41][42][43][44][45]; astroglia mainly function as a reservoir of L-dopa that regulates the uptake or release of L-dopa depending on extracellular L-dopa concentration, but are less capable of converting L-dopa to dopamine [46]. The effect L-dopa on ROS production is debatable.…”

Section: Discussionmentioning

confidence: 99%

l-Dopa and Fluoxetine Upregulate Astroglial 5-HT2B Receptors and Ameliorate Depression in Parkinson’s Disease Mice

Song

Verkhratsky

et al. 2018

Neuroglia

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Here, we report the association between depressive behavior (anhedonia) and astroglial expression of 5-hydroxytryptamine receptor 2B (5-HT2B) in an animal model of Parkinson’s disease, induced by bilateral injection of 6-hydroxydopamine (6-OHDA) into the striatum. Expression of the 5-HT2B receptor at the mRNA and protein level was decreased in the brain tissue of 6-OHDA-treated animals with anhedonia. Expression of the 5-HT2B receptor was corrected by four weeks treatment with either l-3,4-dihydroxyphenylalanine (l-dopa) or fluoxetine. Simultaneously, treatment with l-dopa abolished 6-OHDA effects on both depressive behavior and motor activity. In contrast, fluoxetine corrected 6-OHDA-induced depression but did not affect 6-OHDA-induced motor deficiency. In addition, 6-OHDA downregulated gene expression of the 5-HT2B receptor in astrocytes in purified cell culture and this downregulation was corrected by both l-dopa and fluoxetine. Our findings suggest that 6-OHDA-induced depressive behavior may be related to the downregulation of gene expression of the 5-HT2B receptor but 6-OHDA-induced motor deficiency reflects, arguably, dopamine depletion. Previously, we demonstrated that fluoxetine regulates gene expression in astrocytes by 5-HT2B receptor-mediated transactivation of epidermal growth factor receptor (EGFR). However, the underlying mechanism of l-dopa action remains unclear. The present work indicates that the decrease of gene expression of the astroglial 5-HT2B receptor may contribute to development of depressive behavior in Parkinson’s disease.

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“…In other words, administered L-DOPA results in a marked increase of free DA and DA quinone, leading to a specific PD pathological condition of increased number of activated astrocytes. Since it has been previously reported that astrocytes take up DA [39, 40] and L-DOPA [82,96], and that the aromatic L-amino acid decarboxylase that converts L-DOPA to DA exists in astrocytes [43,54], administered L-DOPA is possibly converted to harmful free DA by activated astrocytes. It is thought that large doses of L-DOPA prescribed for PD patients result over a long period in not only DA cell death, but also in DA cell disorder leading to permanent neuron network remodelling.…”

Section: ■ the Possibility Of Excessive Free Da Promoting Neuron Degementioning

confidence: 99%

L-DOPA treatment from the viewpoint of neuroprotection

et al. 2005

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With regard to the mechanism of selective dopaminergic neuronal death, experimental results of studies on the neurotoxicity of MPTP and rotenone indicate that degeneration of dopamine neurons is closely related to mitochondrial dysfunction, inflammatory process and oxidative stress, particularly with regard to the generation of quinones as dopamine neuron-specific oxidative stress. Thus, it is now clear that the presence of high levels of discompartmentalized free dopamine in dopaminergic neurons may explain the specific vulnerability of dopaminergic neurons through the generation of highly toxic quinones.

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Characterization of L-DOPA transport in cultured rat and mouse astrocytes

Cited by 45 publications

References 28 publications

Resveratrol Alleviates Levodopa-Induced Dyskinesia in Rats

Resveratrol Alleviates Levodopa-Induced Dyskinesia in Rats

l-Dopa and Fluoxetine Upregulate Astroglial 5-HT2B Receptors and Ameliorate Depression in Parkinson’s Disease Mice

L-DOPA treatment from the viewpoint of neuroprotection

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