scholarly journals In vivo Evidence for Cerebral Depletion in High-Energy Phosphates in Progressive Supranuclear Palsy

2009 ◽  
Vol 29 (4) ◽  
pp. 861-870 ◽  
Author(s):  
Maria Stamelou ◽  
Ulrich Pilatus ◽  
Alexander Reuss ◽  
Jörg Magerkurth ◽  
Karla M Eggert ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Basal Ganglia ◽  
Progressive Supranuclear Palsy ◽  
Inorganic Phosphate ◽  
High Energy ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Mitochondrial Energy Metabolism ◽  
Neuronal Marker

Indirect evidence from laboratory studies suggests that mitochondrial energy metabolism is impaired in progressive supranuclear palsy (PSP), but brain energy metabolism has not yet been studied directly in vivo in a comprehensive manner in patients. We have used combined phosphorus and proton magnetic resonance spectroscopy to measure adenosine-triphosphate (ATP), adenosine-diphosphate (ADP), phosphorylated creatine, unphosphorylated creatine, inorganic phosphate and lactate in the basal ganglia and the frontal and occipital lobes of clinically probable patients ( N= 21; PSP stages II to III) and healthy controls ( N= 9). In the basal ganglia, which are severely affected creatine in PSP patients, the concentrations of high-energy phosphates (= ATP + phosphorylated creatine) and inorganic phosphate, but not low-energy phosphates (=ADP+ unphosphorylated creatine), were decreased. The decrease probably does not reflect neuronal death, as the neuronal marker N-acetylaspartate was not yet significantly reduced in the early-stage patients examined. The frontal lobe, also prone to neurodegeneration in PSP, showed similar alterations, whereas the occipital lobe, typically unaffected, showed less pronounced alterations. The levels of lactate, a product of anaerobic glycolysis, were elevated in 35% of the patients. The observed changes in the levels of cerebral energy metabolites in PSP are consistent with a functionally relevant impairment of oxidative phosphorylation.

scholarly journals Comparison of the Effects of Cyclosporin a on the Metabolism of Perfused Rat Brain Slices during Normoxia and Hypoxia

2002 ◽  
Vol 22 (3) ◽  
pp. 342-352 ◽  
Author(s):  
Natalie Serkova ◽  
Paul Donohoe ◽  
Sven Gottschalk ◽  
Carsten Hainz ◽  
Claus U. Niemann ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Cyclosporin A ◽  
Rat Brain ◽  
Ex Vivo ◽  
Brain Slices ◽  
High Energy ◽  
Metabolic Effects ◽  
Resonance Spectroscopy ◽  
Buffer Solution ◽  
Mitochondrial Energy Metabolism

The authors evaluated and compared the metabolic effects of cyclosporin A in the rat brain during normoxia and hypoxia/reperfusion. Ex vivo31P magnetic resonance spectroscopy experiments based on perfused rat brain slices showed that under normoxic conditions, 500 μg/L cyclosporin A significantly reduced mitochondrial energy metabolism (nucleotide triphosphate, 83 ± 9% of controls; phosphocreatine, 69 ± 9%) by inhibition of the Krebs cycle (glutamate, 77 ± 5%) and oxidative phosphorylation (NAD+, 65 ± 14%) associated with an increased generation of reactive oxygen species (285 ± 78% of control). However, the same cyclosporin A concentration (500 μg/L) was found to be the most efficient concentration to inhibit the hypoxia-induced mitochondrial release of Ca2+ in primary rat hippocampal cells with cytosolic Ca2+ concentrations not significantly different from normoxic controls. Addition of 500 μg/L cyclosporin A to the perfusion medium protected high-energy phosphate metabolism (nucleotide triphosphate, 11 ± 15% of control vs. 35 ± 9% with 500 μg/L cyclosporin A) and the intracellular pH (6.2 ± 0.1 control vs. 6.6 ± 0.1 with cyclosporin A) in rat brain slices during 30 minutes of hypoxia. Results indicate that cyclosporin A simultaneously decreases and protects cell glucose and energy metabolism. Whether the overall effect was a reduction or protection of cell energy metabolism depended on the concentrations of both oxygen and cyclosporin A in the buffer solution.

scholarly journals Effects of the mycelial extract of cultured Cordyceps sinensis on in vivo hepatic energy metabolism and blood flow in dietary hypoferric anaemic mice

2000 ◽  
Vol 83 (2) ◽  
pp. 197-204 ◽  
Author(s):  
N. Manabe ◽  
Y. Azuma ◽  
M. Sugimoto ◽  
K. Uchio ◽  
M. Miyamoto ◽  
...  
Keyword(s):  
Blood Flow ◽  
Energy Metabolism ◽  
Nmr Spectroscopy ◽  
Inorganic Phosphate ◽  
Energy State ◽  
High Energy ◽  
Cordyceps Sinensis ◽  
H Nmr ◽  
Hepatic Energy Metabolism

The beneficial effects of a traditional Chinese medicine, Cordyceps sinensis (Cs), on mice with hypoferric anaemia were evaluated by NMR spectroscopy. Experimental hypoferric anaemia was induced in mice by feeding with an Fe-free diet for 6 weeks. They were then given extract from cultured Cs (200 mg/kg body weight daily, orally) and were placed on an Fe-containing recovery diet (35 mg Fe/kg diet) for 4 weeks. In vivo31P and 2H NMR spectra acquired noninvasively and quantitatively at weekly intervals were used to evaluate hepatic energy metabolism and blood flow in the mice. During the 4-week Cs-extract treatment, consistent increases were observed in liver β-ATP: inorganic phosphate value by liver 31P NMR spectroscopy, representing the high energy state, and in blood-flow rate as determined by 2H NMR spectroscopy of deuterated water (D2O) uptake after intravenous injection of D2O. The haematological variables (the packed cell volume and the haemoglobin level) and the hepatic intracellular pH, which was determined from the NMR chemical shift difference between the inorganic phosphate peak and the α-phosphate peak of ATP, were not significantly different between Cs-extract-treated and control mice. As blood flow and energy metabolism are thought to be linked, the Cs-extract-increased hepatic energy metabolism in the dietary hypoferric anaemic mice was concluded to be due to increased hepatic blood flow.

scholarly journals Effect of Dihydroergocristine on Energy Metabolism Studied in the Isolated Perfused Rat Brain Affected by Ischemia and in Neuroblastoma Cells Deprived of Oxygen and Glucose

1984 ◽  
Vol 4 (4) ◽  
pp. 610-614 ◽  
Author(s):  
A. Rachman ◽  
L. Kellmann ◽  
J. Krieglstein
Keyword(s):  
Energy Metabolism ◽  
Rat Brain ◽  
Energy State ◽  
Cell Metabolism ◽  
Neuroblastoma Cells ◽  
Creatine Phosphate ◽  
High Energy ◽  
High Energy Phosphates ◽  
Isolated Perfused Rat Brain

The effect of dihydroergocristine on energy metabolism was studied in the isolated perfused rat brain affected by ischemia and in cultivated C-1300 neuroblastoma cells deprived of oxygen and glucose. Creatine phosphate, ATP, ADP, AMP, glucose, glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, pyruvate, and lactate were measured enzymatically. After a perfusion period of 30 min, the cortex of the isolated perfused rat brain exhibited an energy state not different from that in vivo. Dihydroergocristine added to the perfusion medium (5 μmol/L) did not influence these substrate levels under normal perfusion conditions. However, this drug was able to retard the breakdown of high-energy phosphates during ischemia and to accelerate the restoration of the energy state during the postischemic reperfusion period. The perfusion rate was not changed by the drug, and therefore it was assumed that dihydroergocristine could act directly on cell metabolism. This view was supported by the results obtained from experiments using cultivated N-2a neuroblastoma cells. These cells were incubated in a buffered salt solution deprived of glucose and oxygen for 15 min. Under these conditions, dihydroergocristine (2 μmol/L) added to the incubation medium caused changes in the concentrations of the high-energy phosphates similar to those in the isolated brain preparation: It increased the ATP concentration and decreased the ADP concentration significantly.

High-energy phosphates and tension production in rabbit tibialis anterior/extensor digitorum longus muscles

1997 ◽  
Vol 82 (3) ◽  
pp. 1024-1024 ◽  
Author(s):  
T. W. Ryschon ◽  
J. C. Jarvis ◽  
S. Salmons ◽  
R. S. Balaban
Keyword(s):  
Tibialis Anterior ◽  
Extensor Digitorum Longus ◽  
Energy State ◽  
Oxidative Capacity ◽  
High Energy ◽  
Extensor Digitorum ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Control Muscle

Ryschon, T. W., J. C. Jarvis, S. Salmons, and R. S. Balaban.High-energy phosphates and tension production in rabbit tibialis anterior/extensor digitorum longus muscles. J. Appl. Physiol. 82(3): 1024–1029, 1997.—The effects of repetitive muscle contraction on energy state and tension production were studied in rabbit tibialis anterior/extensor digitorum longus muscles that had been subjected to 90 days of continuous indirect electrical stimulation at 10 Hz. Anesthetized chronically stimulated and control rabbits were challenged with 15 min of stimulation at 4 and 15 tetani/min. Pi-to-phosphocreatine (PCr) ratio (Pi/PCr) was measured in vivo before, during, and after acute stimulation by31P-magnetic resonance spectroscopy, and tension was recorded at the same time. Although Pi/PCr was low at rest, it was significantly higher in chronically stimulated muscle than in control muscle (0.20 ± 0.02 vs. 0.05 ± 0.01, P < 0.05). Stimulation of control muscle for 15 min at both 4 and 15 tetani/min induced a significant rise in Pi/PCr, whereas the same conditions in chronically stimulated muscle did not produce any significant departure from initial levels. The tension produced by control muscle fell to 93 ± 3% of its initial value during stimulation at 4 tetani/min and to 61 ± 7% at 15 tetani/min, respectively. In chronically stimulated muscle, on the other hand, tension was potentiated above its initial level at both stimulation rates (135 ± 15 and 138 ± 11%, respectively) and remained significantly elevated throughout each trial. The ability of chronically stimulated muscle to sustain high levels of activity with minimal perturbations in Pi/PCr or decrement in tension is attributable to cellular adaptations that include a well-documented increase in oxidative capacity.

Oxygen delivery does not limit cardiac performance during high work states

1999 ◽  
Vol 277 (1) ◽  
pp. H50-H57 ◽  
Author(s):  
Jianyi Zhang ◽  
Yo Murakami ◽  
Yi Zhang ◽  
Yong K Cho ◽  
Yun Ye ◽  
...  
Keyword(s):  
Coronary Occlusion ◽  
Coronary Artery Occlusion ◽  
Creatine Phosphate ◽  
High Energy ◽  
Artery Occlusion ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Myocardial Oxygenation ◽  
High Work

This study tested the hypothesis that the loss of myocardial high-energy phosphates (HEP), which occurs during high cardiac work states [J. Zhang, D. J. Duncker, Y. Xu, Y. Zhang, G. Path, H. Merkle, K. Hendrich, A. H. L. From, R. Bache, and K. Uğurbil. Am. J. Physiol. 268: ( Heart Circ. Physiol. 37): H1891–H1905, 1995], is not the result of insufficient intracellular O2 availability. To evaluate the state of myocardial oxygenation, the proximal histidine signal of deoxymyoglobin (Mb-δ) was determined with1H nuclear magnetic resonance spectroscopy (MRS), whereas HEP were examined with31P MRS. Normal dogs ( n = 11) were studied under basal conditions and during combined infusion of dobutamine and dopamine (20 μg ⋅ kg−1 ⋅ min−1iv each), which increased rate-pressure products to >50,000 mmHg ⋅ beats ⋅ min−1. Creatine phosphate (CP) was expressed as CP/ATP, and myocardial myoglobin desaturation was normalized to the Mb-δ resonance present during total coronary artery occlusion. This Mb-δ resonance appeared at 71 parts per million downfield from the water resonance. CP/ATP decreased from 2.22 ± 0.12 during the basal state to 1.83 ± 0.09 during the high work state ( P < 0.01), whereas ΔPi/CP increased from 0 to 0.21 ± 0.04 ( P < 0.01). Despite these HEP changes, Mb-δ remained undetectable. In contrast, when a coronary stenosis was applied to produce a similar decrease in CP/ATP, Mb-δ reached 0.38 ± 0.10 of the value present during total coronary occlusion. These data demonstrate that Mb-δ is readily detected in vivo during limitation of coronary blood flow sufficient to cause a decrease of myocardial CP/ATP. However, similar HEP changes that occur at high work states in the absence of coronary occlusion are not associated with a detectable Mb-δ resonance. The findings support the hypothesis that the myocardial HEP changes observed at high work states are not due to inadequate O2 availability to the mitochondria and emphasize the limitations of interpreting HEP alterations in the absence of knowing the level of myocyte oxygenation.

scholarly journals Effects of Hypoxic Hypoxia on Cerebral Phosphate Metabolites and pH in the Anesthetized Infant Rabbit

1985 ◽  
Vol 5 (4) ◽  
pp. 512-516 ◽  
Author(s):  
Ricardo González-Méndez ◽  
Ann McNeill ◽  
George A. Gregory ◽  
Susan D. Wall ◽  
Charles A. Gooding ◽  
...  
Keyword(s):  
High Energy ◽  
Hypoxic Hypoxia ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
High Energy Phosphate ◽  
Arterial Blood ◽  
A Value ◽  
Venous Infusion ◽  
The Brain

The effects of hypoxic hypoxia on high-energy phosphate metabolites and intracellular pH (pHi) in the brain of the anesthetized infant rabbit were studied in vivo using 31P nuclear magnetic resonance spectroscopy. Five 10- to 16-day-old rabbits were anesthetized with 1.5% halothane. Ventilation was controlled to maintain normocarbia. Inspired O2 fraction was adjusted to produce three states of arterial oxygenation: hyperoxia (Pao2 > 250 mm Hg), normoxia (Pao2 ∼ 100 mm Hg), and hypoxia (Pao2 25–30 mm Hg). During hypoxia, blood pressure was kept within 20% of control values with a venous infusion of epinephrine. During hyperoxia, the phosphocreatine-to-ATP ratio was 0.86, a value that is 2–2.5 times less than that reported for adults. During normoxia, ATP decreased by 20% and Pi increased by 90% from hyperoxia values. During 60 min of hypoxia, the concentrations of high-energy phosphate metabolites did not change, but intracellular and arterial blood pH (pHa) decreased significantly. When hyperoxia was reestablished, pHi returned to normal and pHa remained low. These results suggest that during periods of hypoxemia, the normotensive infant rabbit maintains intracellular concentrations of cerebral high-energy phosphates better than has been reported for adult animals.

Inorganic phosphate as regulator of adenosine formation in isolated guinea pig hearts

1997 ◽  
Vol 272 (2) ◽  
pp. H913-H920 ◽  
Author(s):  
M. W. Gorman ◽  
M. X. He ◽  
C. S. Hall ◽  
H. V. Sparks
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Guinea Pig ◽  
Inorganic Phosphate ◽  
High Energy ◽  
Adenosine Kinase ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Adenosine Release ◽  
Norepinephrine Infusion ◽  
Important Regulator

This study evaluated cytosolic P(i) as an independent regulator of cardiac adenosine formation by dissociating changes in P(i) from changes in AMP and ADP. Myocardial high-energy phosphates (HEP), measured by (31)P nuclear magnetic resonance spectroscopy, were depleted acutely by perfusing isolated guinea pig hearts with 2-deoxyglucose (2-DG), and the effects of 2-DG were compared with a norepinephrine infusion producing similar changes in HEP. 2-DG treatment resulted in lower adenosine release (R(ado)) (54 +/- 18 vs. 622 +/- 199 pmol x min(-1) x g(-1)) and P(i) concentration ([P(i)]) (0.5 +/- 0.1 vs. 6.0 +/- 0.9 mM) than norepinephrine despite similar AMP concentration ([AMP]). Chronic phosphocreatine depletion produced by beta-guanidinopropionic acid feeding also reduced R(ado) and P(i) during hypoxia. Replacement of perfusate glucose and pyruvate with acetate increased R(ado) (from 39 +/- 12 to 356 +/- 100 pmol x min(-1) x g(-1)) and [P(i)] (from 2.0 +/- 0.5 to 5.1 +/- 0.6 mM) with no change in cytosolic [AMP]. Adenosine kinase isolated from guinea pig hearts was inhibited by [P(i)] values seen during hypoxia or hypoperfusion. We conclude that cytosolic [P(i)] can be an important regulator of cardiac adenosine formation through inhibition of adenosine kinase.

scholarly journals In Vivo Mitochondrial Function in Idiopathic and Genetic Parkinson’s Disease

Metabolites ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 19
Author(s):  
Gabriele Dossi ◽  
Letizia Squarcina ◽  
Mario Rango
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Gene Mutation ◽  
High Energy ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
31P Mrs ◽  
Pink1 Gene

Parkinson’s disease (PD) is associated with brain mitochondrial dysfunction. High-energy phosphates (HEPs), which rely on mitochondrial functioning, may be considered potential biomarkers for PD. Phosphorus magnetic resonance spectroscopy (31P-MRS) is a suitable tool to explore in vivo cerebral energetics. We considered 10 31P-MRS studies in order to highlight the main findings about brain energetic compounds in patients affected by idiopathic PD and genetic PD. The studies investigated several brain areas such as frontal lobes, occipital lobes, temporoparietal cortex, visual cortex, midbrain, and basal ganglia. Resting-state studies reported contrasting results showing decreased as well as normal or increased HEPs levels in PD patients. Functional studies revealed abnormal PCr + βATP levels in PD subjects during the recovery phase and abnormal values at rest, during activation and recovery in one PD subject with PINK1 gene mutation suggesting that mitochondrial machinery is more impaired in PD patients with PINK1 gene mutation. PD is characterized by energetics impairment both in idiopathic PD as well as in genetic PD, suggesting that mitochondrial dysfunction underlies the disease. Studies are still sparse and sometimes contrasting, maybe due to different methodological approaches. Further studies are needed to better assess the role of mitochondria in the PD development.

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