glycogen and Memory-Disorders

Normally noradrenaline release ~30 min after training in the day-old chick is essential for memory consolidation by simultaneously increasing both glycogenolysis, by its stimulation of β2-adrenergic (AR) receptors, and glycogen synthesis, by its stimulation of α2-AR receptors in astrocytes. At the same time noradrenaline stimulation of β3-AR receptors increases glucose uptake solely in astrocytes. Intracerebral injection of small oligomeric β-amyloid protein (Aβ1-42) (Aβ) 45 min before one-trial bead discrimination learning in day-old chicks abolishes consolidation of memory 30 min post-learning. The ensuing memory loss can be rescued by injection of selective β3- and β(2-AR agonists (CL316243 and zinterol), which also have the ability to consolidate weakly-reinforced learning into long-term memory. However, although CL316243 rescues Aβ-induced memory loss over a similar time period to when it consolidates weak learning (up to 25 min post training), zinterol is effective over a more limited time period and unexpectedly it does not rescue at the time it promotes glycogenolysis. Injection of Aβ into the hippocampus and the locus coeruleus (LoC) also produces similar memory deficits and injection of both AR agonists into a cortical area can rescue memory from LoC Aβ. We have previously shown that β3-AR stimulation increases astrocytic glucose uptake and have suggested there may be sensitization or upregulation of the receptor. Since β2-AR stimulation does not rescue memory at the time it promotes glycogenolysis, but the receptor does not appear to be impaired, it is suggested that Aβ may be causing an impairment in the synthesis of readily available glycogen.

Topics: Adrenergic beta-2 Receptor Agonists; Adrenergic beta-3 Receptor Agonists; Alzheimer Disease; Amyloid beta-Peptides; Animals; Astrocytes; Chickens; Dioxoles; Ethanolamines; Glucose; Glycogen; Glycogen Synthase Kinase 3; Glycogenolysis; Hippocampus; Locus Coeruleus; Memory Disorders; Memory, Long-Term; Models, Neurological; Peptide Fragments; Receptors, Adrenergic, beta-2; Time Factors

Inhibition of glycogen breakdown blocks memory formation in young animals, but it stimulates the maintenance of the long-term potentiation, a cellular mechanism of memory formation, in hippocampal slices of old animals. Here, we report that a 2-week treatment with glycogen phosphorylase inhibitor BAY U6751 alleviated memory deficits and stimulated neuroplasticity in old mice. Using the 2-Novel Object Recognition and Novel Object Location tests, we discovered that the prolonged intraperitoneal administration of BAY U6751 improved memory formation in old mice. This was accompanied by changes in morphology of dendritic spines in hippocampal neurons, and by "rejuvenation" of hippocampal proteome. In contrast, in young animals, inhibition of glycogen degradation impaired memory formation; however, as in old mice, it did not alter significantly the morphology and density of cortical dendritic spines. Our findings provide evidence that prolonged inhibition of glycogen phosphorolysis improves memory formation of old animals. This could lead to the development of new strategies for treatment of age-related memory deficits.

Topics: Animals; Cognition; Dendritic Spines; Glycogen; Glycogen Phosphorylase; Hippocampus; Memory Disorders; Mice

Ageing is characterized by the development of persistent pro-inflammatory responses that contribute to atherosclerosis, metabolic syndrome, cancer and frailty

Topics: Adult; Aged; Aging; Animals; Cell Respiration; Cells, Cultured; Cognitive Dysfunction; Dinoprostone; Energy Metabolism; Glucose; Glycogen; Humans; Inflammation; Macrophages; Memory Disorders; Mice; Microglia; Mitochondria; Myeloid Cells; Receptors, Prostaglandin E, EP2 Subtype; Signal Transduction; Spatial Memory

A 48 year old woman is described who presented with increasing muscular rigidity and who was found to have a mediastinal tumour. Electrophysiological studies revealed that the muscular stiffness resulted from very high frequency motor unit activity which outlasted voluntary effort, and which was abolished by nerve block. The abnormal activity may have arisen at the anterior horn cell level. Marked improvement followed the administration of diphenylhydantoin.

Topics: Anterior Horn Cells; Electromyography; Electrophysiology; Female; Glycogen; Humans; Lipid Metabolism; Mediastinal Neoplasms; Memory Disorders; Middle Aged; Muscle Contraction; Muscle Rigidity; Muscles; Neural Conduction; Neuromuscular Diseases; Phenytoin