glycogen and Schizophrenia

Glycogen phosphorylase (PG) is a key enzyme taking part in the first step of glycogenolysis. Muscle glycogen phosphorylase (PYGM) differs from other PG isoforms in expression pattern and biochemical properties. The main role of PYGM is providing sufficient energy for muscle contraction. However, it is expressed in tissues other than muscle, such as the brain, lymphoid tissues, and blood. PYGM is important not only in glycogen metabolism, but also in such diverse processes as the insulin and glucagon signaling pathway, insulin resistance, necroptosis, immune response, and phototransduction. PYGM is implicated in several pathological states, such as muscle glycogen phosphorylase deficiency (McArdle disease), schizophrenia, and cancer. Here we attempt to analyze the available data regarding the protein partners of PYGM to shed light on its possible interactions and functions. We also underline the potential for zebrafish to become a convenient and applicable model to study PYGM functions, especially because of its unique features that can complement data obtained from other approaches.

Topics: Animals; Disease Models, Animal; Gene Expression Regulation; Glycogen; Glycogen Phosphorylase; Glycogen Storage Disease Type V; Humans; Insulin Resistance; Light Signal Transduction; Muscle Contraction; Muscle, Skeletal; Necroptosis; Neoplasms; Protein Interaction Mapping; Retinal Pigment Epithelium; Schizophrenia; Zebrafish

Neurodegenerative and psychiatric disorders including Alzheimer's, Parkinson's or Huntington's diseases and schizophrenia have been associated with a deficit in glutathione (GSH). In particular, a polymorphism in the gene of glutamate cysteine ligase modulatory subunit (GCLM) is associated with schizophrenia. GSH is the most important intracellular antioxidant and is necessary for the removal of reactive by-products generated by the utilization of glucose for energy supply. Furthermore, glucose metabolism through the pentose phosphate pathway is a major source of NADPH, the cofactor necessary for the regeneration of reduced glutathione. This study aims at investigating glucose metabolism in cultured astrocytes from GCLM knockout mice, which show decreased GSH levels. No difference in the basal metabolism of glucose was observed between wild-type and knockout cells. In contrast, glycogen levels were lower and its turnover was higher in knockout astrocytes. These changes were accompanied by a decrease in the expression of the genes involved in its synthesis and degradation, including the protein targeting to glycogen. During an oxidative challenge induced by tert-Butylhydroperoxide, wild-type cells increased their glycogen mobilization and glucose uptake. However, knockout astrocytes were unable to mobilize glycogen following the same stress and they could increase their glucose utilization only following a major oxidative insult. Altogether, these results show that glucose metabolism and glycogen utilization are dysregulated in astrocytes showing a chronic deficit in GSH, suggesting that alterations of a fundamental aspect of brain energy metabolism is caused by GSH deficit and may therefore be relevant to metabolic dysfunctions observed in schizophrenia.

Topics: Animals; Antioxidants; Astrocytes; Blotting, Western; Carbon Dioxide; Cells, Cultured; Chronic Disease; Energy Metabolism; Glucose; Glutamate-Cysteine Ligase; Glutathione; Glycogen; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Degeneration; Oxidative Stress; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Schizophrenia

In schizophrenic depressive patients the cytochemical investigation of blood leukocytes revealed the decreased glycogen content as compared with healthy subjects. The activity of some oxidation-reduction and carbohydrate-energy metabolism enzymes was also changed. These cytochemical indices were close to normal levels in patients with circular depression pattern at the pronounced remission stage. These indices can be used in laboratory tests assessing the degree of psychic deterioration.

Topics: Adult; Affective Disorders, Psychotic; Enzymes; Fructose-Bisphosphate Aldolase; Glucosephosphate Dehydrogenase; Glycogen; Humans; L-Lactate Dehydrogenase; Leukocytes; Middle Aged; Monoamine Oxidase; Phosphorylases; Schizophrenia; Succinate Dehydrogenase

The paper is concerned with the results of a study on the morpho-functional state of the thyroid gland and hypophysis. The research material was obtained during the period of 20 min.--5 hours post mortem. Irrespective of the type of the course of schizophrenia it was characterized by signs of deterioration in the functional activity of the thyroid gland. However, it was established that the morphological picture can also be changed under the influence of acutely developing diseases, previous to death. In these cases the morphological picture corresponds to the sufficiently expressed activation of the glands (according to the type of stress-reactions). The author comes to the conclusion of certain functional traits in the morphological changes found in the thyroid gland and hypophysis in schizophrenia.

Topics: Adult; Aged; Glycogen; Histocytochemistry; Humans; Middle Aged; Pituitary Gland; Pituitary Gland, Anterior; Schizophrenia; Thyroid Gland

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Glycogen; Humans; Leukocytes; Liver Glycogen; Oxidoreductases; Peroxidases; Rats; Schizophrenia; Succinate Dehydrogenase; Transferases

Topics: Acute Disease; Adenosine Triphosphatases; Adult; Chronic Disease; Clinical Enzyme Tests; Glycogen; Glycolysis; Humans; Leukocytes; Middle Aged; Phosphorus; Schizophrenia; Transferases

Topics: Animals; Brain; Carbohydrate Metabolism; Glycogen; Humans; Insulin; Lactates; Rats; Schizophrenia; Stimulation, Chemical