Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study was to examine the total, as well as the active form of glycogen phosphorylase in the rat cerebral cortex during development, and to assess the response of the enzyme to induced seizures. Seizures were induced in 7-, 12- and 18-day-old male Wistar rats by i.p. administration of DL-homocysteine thiolactone HCl. Total glycogen phosphorylase activity increased from 54.76 + 2.33 to 181.14 +/- 5.79 micromol/g/h and phosphorylase a from 3.45 +/- 0.45 to 63.73 +/- 1.41 micromol/g/h, from postnatal day 7 to 18, respectively. In 7-day-old pups phosphorylase a corresponded to only 6% of total activity. At the onset of seizures a marked rise (34-90%) in active phosphorylase occurred in all age groups. Thus, in the brains of immature animals a rapid conversion of phosphorylase b to a can occur in response to increased cellular activity. However, in 7-day-old rats, in spite of marked activation, phosphorylase a remained very low (6.0 +/- 0.42 micromol/g/h) and can thus explain the slow onset of glycogenolysis in this age group. Cyclic AMP levels remained unchanged at the onset of seizures in 7- and 12-day-old pups, and only a mild (+ 25%) rise was observed in 18-day-old rats. The marked increase of phosphorylase a in 7- and 12-day-old rats thus occurred in the presence of unchanged levels of cAMP, suggesting the involvement of cAMP-independent mechanism of activation, in which Ca2+ most probably plays a role.
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PMID:Glycogen phosphorylase activity in the cerebral cortex of rats during development: effect of homocysteine-induced seizures. 897 35

During intense cerebral activation approximately half of the glucose plus lactate taken up by the human brain is not oxidized and could replenish glycogen deposits, but the human brain glycogen concentration is unknown. In patients with temporal lobe epilepsy, undergoing curative surgery, brain biopsies were obtained from pathologic hippocampus (n=19) and from apparently 'normal' cortical grey and white matter. We determined the in vivo brain glycogen level and the activity of glycogen phosphorylase and synthase. Regional differences in glycogen concentration were examined similarly in healthy pigs (n=5). In the patients, the glycogen concentration in 'normal' grey and white matter was 5 to 6 mmol/L, but much higher in the hippocampus, 13.1+/-4.3 mmol/L (mean+/-s.d.; P<0.001); the activities of glycogen phosphorylase and synthase displayed the same pattern. In normal hippocampus from pigs, glycogen was similarly higher than in grey and white matter. Consequently, in human grey and white matter and, particularly, in the hippocampus of patients with temporal lope epilepsy, glycogen constitutes a large, active energy reserve, which may be of importance for energy provision during sustained synaptic activity as epileptic seizures.
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PMID:High glycogen levels in the hippocampus of patients with epilepsy. 1713 25

Glial cells provide energy substrates to neurons, in part from glycogen metabolism, which is influenced by glycogen phosphorylase (GP). To gain insight into the potential subfield and laminar-specific expression of GP, histochemistry can be used to evaluate active GP (GPa) or totalGP (GPa + GPb). Using this approach, we tested the hypothesis that changes in GP would occur under pathological conditions that are associated with increased energy demand, i.e. severe seizures (status epilepticus or 'status'). We also hypothesized that GP histochemistry would provide insight into changes in the days and weeks after status, particularly in the hippocampus and entorhinal cortex, where there are robust changes in structure and function. One hour after the onset of pilocarpine-induced status, GPa staining was reduced in most regions of the hippocampus and entorhinal cortex relative to saline-injected controls. One week after status, there was increased GPa and totalGP, especially in the inner molecular layer, where synaptic reorganization of granule cell mossy fibre axons occurs (mossy fibre sprouting). In addition, patches of dense GP reactivity were evident in many areas. One month after status, levels of GPa and totalGP remained elevated in some areas, suggesting an ongoing role of GP or other aspects of glycogen metabolism, possibly due to the evolution of intermittent, recurrent seizures at approximately 3-4 weeks after status. Taken together, the results suggest that GP is dynamically regulated during and after status in the adult rat, and may have an important role in the pilocarpine model of epilepsy.
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PMID:Acute and chronic changes in glycogen phosphorylase in hippocampus and entorhinal cortex after status epilepticus in the adult male rat. 1761 48

The rosuvastatin inducing rhabdomyolysis in McArdle disease (MD) has not been reported to date. A 35-years-old man had exercise intolerance, muscular fatigue and cramps during physical activity since infancy. He presented severe rhabdomyolysis episode with seizure and coma after use of rosuvastatin. The investigation showed increased serum creatine-kinase levels and the forearm ischemic exercise did not increase venous lactate. The muscle biopsy showed subsarcolemmal and central accumulation of glycogen and absence of the myophosphorylase enzyme. The statin induced myopathy is discussed and the danger of its use in MD is emphasized.
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PMID:McArdle disease with rhabdomyolysis induced by rosuvastatin: case report. 1795 91

Glycogen, the largest cytosolic macromolecule, is soluble because of intricate construction generating perfect hydrophilic-surfaced spheres. Little is known about neuronal glycogen function and metabolism, though progress is accruing through the neurodegenerative epilepsy Lafora disease (LD) proteins laforin and malin. Neurons in LD exhibit Lafora bodies (LBs), large accumulations of malconstructed insoluble glycogen (polyglucosans). We demonstrated that the laforin-malin complex reduces LBs and protects neuronal cells against endoplasmic reticulum stress-induced apoptosis. We now show that stress induces polyglucosan formation in normal neurons in culture and in the brain. This is mediated by increased glucose-6-phosphate allosterically hyperactivating muscle glycogen synthase (GS1) and is followed by activation of the glycogen digesting enzyme glycogen phosphorylase. In the absence of laforin, stress-induced polyglucosans are undigested and accumulate into massive LBs, and in laforin-deficient mice, stress drastically accelerates LB accumulation and LD. The mechanism through which laforin-malin mediates polyglucosan degradation remains unclear but involves GS1 dephosphorylation by laforin. Our work uncovers the presence of rapid polyglucosan metabolism as part of the normal physiology of neuroprotection. We propose that deficiency in the degradative phase of this metabolism, leading to LB accumulation and resultant seizure predisposition and neurodegeneration, underlies LD.
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PMID:Laforin prevents stress-induced polyglucosan body formation and Lafora disease progression in neurons. 2354 41

We investigated a control model of hypoglycemia-exposed brain tissues from a small series of patients with insulinoma, immediately dissect them, and perform a differential cold centrifugation to obtain gliosomes and examine alterations of glycogenolytic mechanisms. The BB as well as MM isoforms of glycogen phosphorylase enzymatic protein expression remained unaltered between insulinoma and control subjects within the gliosomes. However, the glycogen phosphorylase remained in a form that was potentially activated several folds on placing the gliosomes in a glucose-free medium. This was examined by its increased interaction with protein kinase A. Inhibitors of glycogen phosphorylase was used as controls. Furthermore, we demonstrated that glucose-depleted medium enhanced production of both ATP and lactate by the gliosomes. It is possible that a portion of glucose obtained from glycogen breakdown was circuited through glycolytic pathways to generate ATP. It has been reported earlier that ATP within gliosomes plays a major role in glutamate uptake, thus potentially preventing seizure during active bouts of hypoglycemia. Lactate shuttle from astrocytes is a potential mechanism to balance neuronal bioenergetics during events of hypoglycemia. Newer approaches to pharmacologically modulate glycogen phosphorylase may prove to be rational approach for neuroprotective therapy in this common clinical syndrome of hypoglycemia.
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PMID:Altered Plasticity of Glycogen Phosphorylase in Forebrain Gliosomes Obtained from Insulinoma Patients. 2594 81

A 35year-old male developed myalgias after moving furniture and was hospitalized with acute renal failure and rhabdomyolysis requiring hemodialysis. He then had several generalized tonic-clonic seizures. Brain MRI showed findings of posterior reversible encephalopathy syndrome (PRES). Interval history revealed easy fatigability and exercise-induced myalgias in childhood but no preceding history of urine discoloration. Quadriceps biopsy showed absent muscle myophosphorylase reactivity consistent with the diagnosis of McArdle disease. With supportive care he improved and the PRES resolved. This case represents an extreme in the spectrum of complications that can occur in McArdle disease, including downstream central nervous system involvement and highlights the importance of early recognition and aggressive management of rhabdomyolysis.
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PMID:PRES leading to the diagnosis of McArdle disease. 2888 83