L-DOPA Uptake in Astrocytic Endfeet Enwrapping Blood Vessels in Rat Brain

Department of Physiology, Universidad Central del Caribe, Bayamón, PR 00956, USA.
Parkinson's disease 07/2012; 2012(27):321406. DOI: 10.1155/2012/321406
Source: PubMed


Astrocyte endfeet surround brain blood vessels and can play a role in the delivery of therapeutic drugs for Parkinson's disease. However, there is no previous evidence of the presence of LAT transporter for L-DOPA in brain astrocytes except in culture. Using systemic L-DOPA administration and a combination of patch clamp, histochemistry and confocal microscopy we found that L-DOPA is accumulated mainly in astrocyte cell bodies, astrocytic endfeet surrounding blood vessels, and pericytes. In brain slices: (1) astrocytes were exposed to ASP(+), a fluorescent monoamine analog of MPP(+); (2) ASP(+) taken up by astrocytes was colocalized with L-DOPA fluorescence in (3) glial somata and in the endfeet attached to blood vessels; (4) these astrocytes have an electrogenic transporter current elicited by ASP(+), but intriguingly not by L-DOPA, suggesting a different pathway for monoamines and L-DOPA via astrocytic membrane. (5) The pattern of monoamine oxidase (MAO type B) allocation in pericytes and astrocytic endfeet was similar to that of L-DOPA accumulation. We conclude that astrocytes control L-DOPA uptake and metabolism and, therefore, may play a key role in regulating brain dopamine level during dopamine-associated diseases. These data also suggest that different transporter mechanisms may exist for monoamines and L-DOPA.

Download full-text


Available from: Legier V Rojas
  • Source
    • "Transporters on neurons and astrocytes clearing neurotransmitters from the synaptic cleft and extracellular space mainly belong to different " secondary transporters " families. Recently, it has been shown that astrocytes and other glial cells accumulate monoamines [1] and polyamines [2] [3] while lacking the enzymes for their synthesis [1, 4–6]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: It is known that secondary transporters, which utilize transmembrane ionic gradients to drive their substrates up a concentration gradient, can reverse the uptake and instead release their substrates. Unfortunately, the Michaelis-Menten kinetic scheme, which is popular in transporter studies, does not include transporter reversal, and it completely neglects the possibility of equilibrium between the substrate concentrations on both sides of the membrane. We have developed a complex two-substrate kinetic model that includes transport reversal. This model allows us to construct analytical formulas allowing the calculation of a “heteroexchange” and “transacceleration” using standard Michaelis coefficients for respective substrates. This approach can help to understand how glial and other cells accumulate substrates without synthesis and are able to release such substrates and gliotransmitters.
    Full-text · Article · Oct 2013 · Journal of Biophysics
  • [Show abstract] [Hide abstract]
    ABSTRACT: Historically, much of the focus on monoamine oxidases and their substrates has been in the area of depression and the monoamine neurotransmitters serotonin (5-hydroxytryptamine), noradrenaline, and to a lesser extent, dopamine. With both forms of monoamine oxidase (A and B), the production of hydrogen peroxide as a byproduct of the reaction between the monoamine oxidases and their monoamine substrates has also implicated monoamine oxidase-sensitive events in intrinsic cell death pathways, particularly those centered on oxidative stress and peroxyradical-mediated mechanisms. Consequently, and perhaps not unexpectedly, the inhibition of monoamine oxidase has been considered as adjunctive therapy in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease, both of which involve a significant oxidative stress component. Yet the literature also provides ambiguities; indeed, not all of the functions of monoamine oxidasesare dependent on catalytic activity nor can they all be ascribed to expression levels of the monoamine oxidase proteinper se. Recent reports strongly suggest that the functions of monoamine oxidases also rely on post-translational modifications, epigenetic influences, interactions with other proteins, the cell phenotype and its localization to specific subcellular compartments. These recent developments certainly complicate the issue, yet they need to be duly considered when implicating monoamine oxidases and their inhibitors in both in vitro and in vivopathological contexts.
    No preview · Article · Nov 2012 · Current topics in medicinal chemistry
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epilepsy mapping with high spatial and temporal resolution has great significance for both fundamental research on epileptic neurons and the clinical management of epilepsy. In this communication, we demonstrate for the first time in vivo epilepsy mapping with high spatial and temporal resolution and dual optical contrasts in an animal model. Through the variations of a depthresolved optical coherence tomography signal with optical scattering contrast, we observed that epileptic neuron activities modulated the optical refractive index of epileptic neurons and their surrounding tissue. Simultaneously, through neurovasculature coupling mechanisms and optical absorption contrast, we used photoacoustic signals to document the hemodynamic changes of the microvasculature surrounding the epileptic neurons. The epilepsy mapping results were confirmed by a simultaneously recorded electroencephalogram signal during epileptic seizure. Our new epilepsy mapping tool, with high temporal and spatial resolution and dual optical contrasts, may find many applications, such as drug development and epilepsy surgery.
    No preview · Article · Apr 2013 · Journal of Neuroscience Methods
Show more

We use cookies to give you the best possible experience on ResearchGate. Read our cookies policy to learn more.