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

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
M. Y. Inyushin ◽  
A. Huertas ◽  
Y. V. Kucheryavykh ◽  
L. Y. Kucheryavykh ◽  
V. Tsydzik ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Brain Slices ◽  
Dopamine Level ◽  
Brain Dopamine ◽  
Therapeutic Drugs ◽  
Dopa Accumulation ◽  
Uptake And Metabolism ◽  
Astrocytic Endfeet ◽  
Dopa Uptake ◽  
Astrocyte Endfeet

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 forL-DOPA in brain astrocytes except in culture. Using systemicL-DOPA administration and a combination of patch clamp, histochemistry and confocal microscopy we found thatL-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 withL-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 byL-DOPA, suggesting a different pathway for monoamines andL-DOPA via astrocytic membrane. (5) The pattern of monoamine oxidase (MAO type B) allocation in pericytes and astrocytic endfeet was similar to that ofL-DOPA accumulation. We conclude that astrocytes controlL-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 andL-DOPA.

scholarly journals EVALUATION OF ANTI-OBESITY EFFECT OF AQUEOUS EXTRACT OF MUCUNA PRURIENS SEEDS ON RATS

2017 ◽  
Vol 9 (3) ◽  
pp. 111
Author(s):  
Javid Mansuri ◽  
Archana Paranjape
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Aqueous Extract ◽  
Density Lipoprotein ◽  
Mucuna Pruriens ◽  
Control Group ◽  
Dopamine Level ◽  
Sprague Dawley ◽  
Brain Dopamine ◽  
Standard Drug

Objective: Evaluation of the anti-obesity effect of aqueous extract of Mucuna pruriens seeds on rats.Methods: Male Sprague-Dawley (SD) rats were subjected to high-fat diet (HFD) for 12 wk. L-DOPA (12.5 mg/kg, p. o.) as standard drug and aqueous extract of Mucuna pruriens (AEMP) seeds (200 mg/kg, p. o. and 400 mg/kg, p. o.) as test drugs were administered in last 4 wk along with HFD. Body weight, food intake, body mass index (BMI), serum total cholesterol (TC), triglyceride (TG) and high-density lipoprotein (HDL) levels were measured at the end of fourth, eighth and twelfth wk, while white adipose tissue (WAT) mass and brain dopamine levels were measured at the end of the twelfth wk.Results: AEMP (200 mg/kg, p. o.) and (400 mg/kg, p. o.) treated groups showed a significant decrease in food intake and weight gain without altering BMI. Moreover, TG levels were lower in treated groups as compared to the HFD group, but no significant changes were observed in TC and HDL levels. L-DOPA-treated group showed a significant decrease in body weight, food intake, BMI and WAT. Both AEMP and L-DOPA-treated groups showed an increase in brain dopamine levels as compared to disease control group (p<0.05).Conclusion: L-DOPA and AEMP showed anti-obesity activity by reducing body weight gains, food intake and WAT weights; modulating TG with increased brain dopamine level which correlates to the inhibitory action of dopamine on reward mechanism. 

Regulatory pathways and uptake ofl-DOPA by capillary cerebral endothelial cells, astrocytes, and neuronal cells

2001 ◽  
Vol 280 (2) ◽  
pp. C333-C342 ◽  
Author(s):  
B. Sampaio-Maia ◽  
M. P. Serrão ◽  
P. Soares-da-Silva
Keyword(s):  
Amino Acid ◽  
Neuroblastoma Cells ◽  
Cell Types ◽  
Amino Acid Transporter ◽  
Nitric Oxide Donor ◽  
Intracellular Camp ◽  
Regulatory Pathways ◽  
Dopa Accumulation ◽  
Acid Transporter ◽  
Dopa Uptake

We examined the nature and regulation of the inwardl-3,4-dihydroxyphenylalanine (l-DOPA) transporter in rat capillary cerebral endothelial (RBE4) cells, type 1 astrocytes (DI TNC1), and Neuro-2a neuroblastoma cells. In all three cell types, the inward transfer of l-DOPA was largely promoted through the 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid-sensitive and sodium-independent L-type amino acid transporter. Only in DI TNC1 cells was the effect of maneuvers that increase intracellular cAMP levels accompanied by increases inl-DOPA uptake. Also, only in DI TNC1 cells was the effect of the guanylyl cyclase inhibitor LY-83583 accompanied by a 65% increase in l-DOPA accumulation, whereas the nitric oxide donor sodium nitroprusside produced a 25% decrease inl-DOPA accumulation. In all three cell types, the Ca2+/calmodulin inhibitors calmidazolium and trifluoperazine inhibited l-DOPA uptake in a noncompetitive manner. Thapsigargin (1 and 3 μM) and A-23187 (1 and 3 μM) failed to alter l-DOPA accumulation in RBE4 and Neuro-2a cells but markedly increased l-DOPA uptake in DI TNC1cells. We concluded that l-DOPA in RBE4, DI TNC1, and Neuro-2a cells is transported through the L-type amino acid transporter and appears to be under the control of Ca2+/calmodulin-mediated pathways. Astrocytes, however, are endowed with other processes that appear to regulate the accumulation of l-DOPA, responding positively to increases in intracellular Ca2+ and cAMP and to decreases in cGMP.

scholarly journals Astrocytic endfeet re-cover blood vessels after removal by laser ablation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hideaki Kubotera ◽  
Hiroko Ikeshima-Kataoka ◽  
Yoshiki Hatashita ◽  
Anna Letizia Allegra Mascaro ◽  
Francesco Saverio Pavone ◽  
...  
Keyword(s):  
Laser Ablation ◽  
Blood Vessels ◽  
Astrocytic Endfeet

Polymer-Encapsulated PC-12 Cells Demonstrate High-Affinity Uptake of Dopamine in Vitro and 18F-DOPA Uptake and Metabolism after Intracerebral Implantation in Nonhuman Primates

1997 ◽  
Vol 6 (5) ◽  
pp. 469-477 ◽  
Author(s):  
Thyagarajan Subramanian ◽  
Dwaine F. Emerich ◽  
Roy A. E. Bakay ◽  
John M. Hoffman ◽  
Mark M. Goodman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc 12 Cells ◽  
In Vivo Experiments ◽  
Positron Emission ◽  
Before And After ◽  
Uptake And Metabolism ◽  
Dopa Uptake

Intracranial implantation of polymer-encapsulated PC-12 cells has been shown to improve motor behavioral performance in animal models of Parkinson's disease. The purpose of this blinded study was to examine whether such improvement is associated with the active uptake and metabolism of dopamine precursors by intracerebrally implanted polymer-encapsulated PC-12 cells. In an in vitro experiment we demonstrate that 3H-dopamine uptake by PC-12 cells was 108 fmol/min × 106 cells, and that this uptake can be specifically blocked 88% by the addition of 10 nM of nomifensine. In the in vivo experiments, polymer-encapsulated PC-12 cells were implanted in four MPTP-treated monkeys into the left deep parietal white matter (R1) or left striatum (R2-4). A fifth MPTP-treated monkey (R5) served as a control and received left striatal implants of empty capsules. 18F-Dopa Positron Emission Tomography (PET) imaging was performed on each monkey before and after implantation surgery by blinded investigators. PET images obtained 5-13 wk after implantation demonstrated well delineated focal areas of high 18F-dopa uptake in R1, R2, and R4. The focal area of high 18F-dopa uptake in R1 precisely coregistered on a brain magnetic resonance image to the site of implantation. R3 (in whom the polymer-encapsulated PC-12 cells demonstrated poor cell survival upon explantation) and R5 (empty capsules) failed to demonstrate any area of increased 18F-dopa uptake in their PET images. Histological examination of the host brain revealed no sprouting of dopaminergic nerve terminals around the implantation sites of the polymer-encapsulated PC-12 cells. These results indicate that the previously noted behavioral improvement after intrastriatal implantation of polymer encapsulated PC-12 cells is at least in part due to their highly specific uptake and metabolism of dopamine precursors. Furthermore, these data suggest that polymer-encapsulated PC-12 cells can store, reuptake, and functionally replenish dopamine and therefore, may be an effective treatment for Parkinson's disease.

scholarly journals Effect of novel phenothiazine derivatives on brain dopamine in Wistar rats

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Chandravadivelu Gopi ◽  
Vedula Girija Sastry ◽  
Magharla Dasaratha Dhanaraju
Keyword(s):  
Body Weight ◽  
Spectroscopic Method ◽  
The Body ◽  
Dopamine Level ◽  
Phenothiazine Derivatives ◽  
Brain Dopamine ◽  
Standard Drug ◽  
Living Things ◽  
Double Beam ◽  
The Brain

Abstract Background Neurotransmitters are involved in several functions in the brain and the body of living things. Changes in the level of neurotransmitters in the brain are associated with several illnesses. Some of the drugs are controlling the neurotransmitter by adjusting the level in the brain and are exclusively used in the treatment of psychological disorders. The purpose of the study was to find out the effect of novel synthesised phenothiazine derivatives (GC1, GC2 and GC8) either alone (7.5 mg/kg or 15 mg/kg, oral) or in combination with amphetamine on the experimental animals. Results Dopamine level in rat brain was estimated by a spectroscopic method using the UV-visible double beam spectrophotometer at 735 nm. The results revealed that these derivatives blocked the brain dopamine level significantly. The compound GC8 (15 mg/kg) significantly reduced the level of dopamine (0.151 ± 0.04, 0.284 ± 0.03) as similar to that of a standard drug. Furthermore, compounds GC2 (15 mg/kg) and GC1 (15 mg/kg) exhibited a varying level of dopamine inhibition level and have been found at 0.203 ± 0.06 μg/ml, 0.302 ± 0.04 μg/ml, 0.234 ± 0.02 μg/ml and 0.318 ± 0.07 μg/ml, respectively, after the administration of these derivatives either alone or in combination with amphetamine. Conclusions The study revealed that the compound 2-amino-6-(3-hydroxy-4-methyl phenyl) pyrimidine-4-yl) (7-chloro-10-(3- (N, N-dimethylamino) propyl)-10H-phenothiazine-3-yl) methanone (GC8, 15 mg/kg) extensively reduced the dopamine level. The order of dopamine-inhibiting effect of the selected compound was found to be GC8 > GC2 > GC1. The increased body weight and relative brain-body weight were also observed in the tested animals due to more intake of food and fluid retention. Graphical abstract

Evidence against leukotrienes as mediators of brain edema

1991 ◽  
Vol 74 (5) ◽  
pp. 773-780 ◽  
Author(s):  
Andreas Unterberg ◽  
Walter Schmidt ◽  
Michael Wahl ◽  
Earl F. Ellis ◽  
Anthony Marmarou ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Brain Edema ◽  
Parietal Cortex ◽  
Brain Slices ◽  
Control Group ◽  
Tissue Water ◽  
Content Type ◽  
Cranial Window ◽  
Fine Print

✓ Leukotrienes are powerful metabolites of arachidonic acid which are known to increase the permeability of peripheral blood vessels. These substances are found in brain tissue in association with cerebral ischemia, and in brain tumors. Therefore, it has been proposed that leukotrienes have a mediator function in brain edema. This hypothesis was subjected to further experimental analysis in this study, in which the authors investigated whether: 1) superfusion of the exposed brain surface with leukotrienes increases the permeability of extraparenchymal blood vessels in vivo; 2) intraparenchymal infusion of leukotrienes induces brain edema; and 3) pharmacological inhibition of leukotriene formation by BW755C, an inhibitor of leukotriene synthesis, reduces formation of brain edema from a standardized traumatic insult. The pial vessels of the parietal cortex of cats were examined by fluorescence microscopy during cerebral superfusion with the leukotrienes C4 (LTC4), D4 (LTD4), or E4 (LTE4) by using an open cranial window preparation. Intravenous Na+-fluorescein served as an in vivo blood-brain barrier (BBB) indicator. Superfusion of the pia with leukotrienes (up to 2 µM) did not open the barrier to fluorescein, but was associated with a significant constriction (up to 25%) of arterial and venous vessels. In experiments with slow infusion of leukotriene B4 (LTB4) or LTC4 into the white matter of feline brain, the tissue water content was subsequently determined in serial brain slices using the specific gravity method. Tissue water profiles obtained after a 15- µM infusion of either LTB4 or LTC4 were virtually identical with those of control animals infused with mock cerebrospinal fluid. Thus, neither LTB4 nor LTC4 led to an augmentation of infusion-induced brain edema. In a final series, a cold lesion of the left parietal cortex was induced in rabbits. Twenty-four hours later, swelling of the exposed hemisphere was quantified by gravimetrical comparison of its weight with that of the contralateral nontraumatized hemisphere. Eight animals received BW755C intravenously prior to and after trauma to inhibit formation of leukotrienes. Seven rabbits were infused with an equivalent volume of saline as a control study. The resulting hemispheric swelling was 7.7% ± 0.6% (mean ± standard error of the mean) 24 hours later in animals receiving BW755C and 7.8% ± 1.2% in the control group, indicating that inhibition of leukotrienes was ineffective in preventing formation of vasogenic brain edema. The findings demonstrate that leukotrienes administered to the brain in concentrations occurring under pathological conditions do not open the BBB nor do they induce brain edema. Moreover, formation of brain edema from a standard insult was not therapeutically influenced by inhibition of leukotriene synthesis. Thus, the current findings taken together do not support a role of leukotrienes as mediators in brain edema.

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