glycogen and Parkinson-Disease

Emerging evidence that autophagy serves as a sweeper for toxic materials in the brain gives us new insight into the pathophysiology of neurodegenerative diseases. Autophagy is important for maintaining cellular homeostasis associated with metabolism. Some neurodegenerative diseases such as Alzheimer׳s and Parkinson׳s diseases are accompanied by altered metabolism and autophagy in the brain. In this review, we discuss how hormones and nutrients regulate autophagy in the brain and affect neurodegeneration. This article is part of a Special Issue entitled SI:Autophagy.

Topics: Alzheimer Disease; Animals; Autophagy; Brain; Cholesterol; Ghrelin; Glucose; Glycogen; Homeostasis; Humans; Inulin; Melatonin; Mice; Neurodegenerative Diseases; Parkinson Disease

Injection of excitotoxins, such as quinolinic acid (QA), into the striatum has been extensively used as an experimental model of Huntington's disease, while injection of 6-hydroxydopamine (6-OHDA) into the dopaminergic nigrostriatal pathway provides a well established model of Parkinson's disease. In the present study, we have examined the metabolic changes induced by an intrastriatal injection of QA or 6-OHDA using histochemical staining for the metabolic markers cytochrome oxidase (COx) and active glycogene phosphorylase (GPa). Intrastriatal injection of QA produced major changes in COx (decrease of staining) and GPa (increase of staining, except in the core of the lesion where the staining was virtually absent) histochemistry at the level of the striatum and of most of the other basal ganglia nuclei. Although attenuated over time, these changes persisted up to one year after the lesion. On the contrary, after the intrastriatal injection of 6-OHDA (which induces only a partial lesion of the nigrostriatal pathway), we did not observe any remarkable changes in COx or GPa staining. This study illustrates the discrepancies between the morphological changes and metabolic changes that are induced when using these experimental models of neurodegenerative disorders.

Topics: Animals; Autoradiography; Benzazepines; Biomarkers; Corpus Striatum; Disease Models, Animal; Dopamine Antagonists; Dopamine Uptake Inhibitors; Electron Transport Complex IV; Glycogen; Huntington Disease; Male; Mazindol; Microinjections; Nerve Degeneration; Oxidopamine; Parkinson Disease; Phosphorylase a; Quinolinic Acid; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Dopamine; Sympatholytics; Tritium

There are no peripheral diagnostic markers for Parkinson's disease (PD). However, recent studies of platelets in PD patients indicate that mitochondrial and monoamine oxidase function may be abnormal. This investigation examines platelets in PD from a morphological standpoint utilizing transmission electron microscopy (EM). Fourteen PD patients (seven treated, seven untreated) and seven age matched controls had platelets separated from other blood components, fixed in a standardized fashion and examined by EM. Platelets (in the activated form because they were collected in glass tubes) were evaluated at magnifications of 15,000x and 40,000x. Abnormalities observed in treated and untreated PD patients included the presence of numerous large intracytoplasmic vacuoles formed from the open canalicular system. Morphometric examination performed at 40,000x magnification indicated that the mean area of vacuoles and the cytoplasmic volume percent of platelets occupied by vacuoles were significantly greater in PD (p < 0.05) than controls. However, differences observed between treated and untreated PD groups suggest that these changes could be caused by the disease or the treatment or both. No abnormalities were found in relation to mitochondria, storage granules and glycogen. From EM assessment, we conclude that platelets in PD are morphologically abnormal.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Platelets; Cytoplasmic Granules; Female; Glycogen; Humans; Male; Microscopy, Electron; Middle Aged; Mitochondria; Parkinson Disease

Parkinson's disease has been associated with defects in oxidative phosphorylation (Oxphos). We analyzed mitochondria isolated from muscle biopsies of 6 patients with Parkinson's disease for deficiencies in Oxphos enzymes and for mutations in the mitochondrial DNA. Oxphos enzyme assays were compared to the 5 to 95% confidence intervals from 16 control subjects. Four patients had complex I defects, whereas 1 patient had a complex IV defect. A genetic basis for Parkinson's disease was suggested by the presence of affected relatives of 2 patients with Parkinson's disease. Known pathological mitochondrial DNA mutations (insertion-deletions or point mutations) were not found. We conclude that Parkinson's disease is a systemic disorder of Oxphos, probably of a complex genetic etiology. Premature cell death in the nigrostriatal dopamine pathway could be due to energetic impairment and accentuated free radical generation caused by an Oxphos defect.

Topics: Adult; Aged; Aging; Biopsy; Child; DNA, Mitochondrial; Female; Glycogen; Humans; Lipids; Male; Middle Aged; Mitochondria, Muscle; Oxidative Phosphorylation; Oxygen Consumption; Parkinson Disease; Polymorphism, Genetic

Parkinsonism was induced in rats by using phenothiazines (Butyrylperazin and Thioproperazin). (P-group), or reserpine, (R-group). [U-14 C)D-glucose was administered when the symptoms of Parkinsonism had become fully developed. Concentrations and radioactivities of different metabolites were studied in brain, liver and blood serum. 1. Both types of treatments resulted in a decrease in the synthesis of amino acids from [14C]glucose in the brain. The concentrations of amino acids and the glycogen remained uneffected. Phenothiazines enhanced the conversion of lipids, while reserpine increased their concentration. 2. Reduced de novo synthesis of amino acids was recorded in the liver. Phenothiazines resulted in the storage of glycogen and lipids; reserpine resulted in the storage of lipids and enhanced the conversion of glycogen. 3. Both treatments caused a fall in the amino acid concentration of the blood serum. A rise in the specific radioactivity of blood amino acids was observed in the P-group, while a decrease in specific radioactivity was observed in the R-group. A hyperglycemia was induced in the R-group with reduced specific radioactivity of glucose in both P-and R-groups. A reduction in lipid concentration of blood serum was achieved with an increased specific radioactivity in P-group and decreased radioactivity in R-group. 4. The changes in amino acids common to both treatments are also observed in human Parkinsonism.

Topics: Amino Acids; Animals; Blood Glucose; Brain; Glucose; Glycogen; Lipid Metabolism; Liver; Liver Glycogen; Parkinson Disease; Phenothiazines; Rats; Reserpine; Tissue Distribution

Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Aged; Blood Flow Velocity; Blood Glucose; Carbon Dioxide; Carbon Radioisotopes; Creatine; Fatty Acids, Nonesterified; Glycogen; Heart Rate; Humans; Lactates; Leg; Male; Middle Aged; Muscles; Myofibrils; Oleic Acids; Oxygen Consumption; Parkinson Disease; Physical Exertion; Plethysmography; Ventilation-Perfusion Ratio

Topics: Animals; Brain; Carbohydrate Metabolism; Dementia; Fructose; Germ-Free Life; Glucose; Glycogen; Glycolysis; Hexokinase; Humans; Hydroxybutyrates; Infusions, Parenteral; Lactates; Male; Mice; Parkinson Disease; Phosphates; Pyruvates