glycogen and Nerve-Degeneration

Topics: Animals; Cats; Cerebellum; Glycogen; Microscopy, Electron; Nerve Degeneration; Nerve Endings; Phagocytosis; Synapses

Topics: Angiokeratoma; Arthritis; Autopsy; Biopsy; Carbohydrate Metabolism, Inborn Errors; Central Nervous System Diseases; Child; Diffuse Cerebral Sclerosis of Schilder; Encephalitis; Encephalomyelitis; Gangliosides; Gaucher Disease; Glycogen; Glycosaminoglycans; Humans; Lipid Metabolism; Lipidoses; Medical History Taking; Metabolic Diseases; Mucopolysaccharidoses; Mucopolysaccharidosis IV; Multiple Sclerosis; Myelin Sheath; Nerve Degeneration; Neurons; Niemann-Pick Diseases; Retinal Degeneration; Slow Virus Diseases; Virus Diseases

The hallmark of Lafora disease, a fatal neurodegenerative disorder, is the accumulation of intracellular glycogen aggregates called Lafora bodies. Until recently, it was widely believed that brain Lafora bodies were present exclusively in neurons and thus that Lafora disease pathology derived from their accumulation in this cell population. However, recent evidence indicates that Lafora bodies are also present in astrocytes. To define the role of astrocytic Lafora bodies in Lafora disease pathology, we deleted glycogen synthase specifically from astrocytes in a mouse model of the disease (malinKO). Strikingly, blocking glycogen synthesis in astrocytes-thus impeding Lafora bodies accumulation in this cell type-prevented the increase in neurodegeneration markers, autophagy impairment, and metabolic changes characteristic of the malinKO model. Conversely, mice that over-accumulate glycogen in astrocytes showed an increase in these markers. These results unveil the deleterious consequences of the deregulation of glycogen metabolism in astrocytes and change the perspective that Lafora disease is caused solely by alterations in neurons.

Topics: Animals; Astrocytes; Brain; Disease Models, Animal; Glycogen; Glycogen Synthase; Lafora Disease; Mice; Mice, Knockout; Nerve Degeneration; Neurons; Ubiquitin-Protein Ligases

Maladaptive responses to stress might play a role in the sensitivity of neurons to stress. To identify novel cellular responses to stress, we performed transcriptional analysis in acutely stressed mouse neurons, followed by functional characterization in Caenorhabditis elegans. In both contexts, we found that the gene GDPGP1/mcp-1 is down-regulated by a variety of stresses. Functionally, the enzyme GDPGP1/mcp-1 protects against stress. Knockdown of GDPGP1 in mouse neurons leads to widespread neuronal cell death. Loss of mcp-1, the single homologue of GDPGP1 in C. elegans, leads to increased degeneration of GABA neurons as well as reduced survival of animals following environmental stress. Overexpression of mcp-1 in neurons enhances survival under hypoxia and protects against neurodegeneration in a tauopathy model. GDPGP1/mcp-1 regulates neuronal glycogen levels, indicating a key role for this metabolite in neuronal stress resistance. Together, our data indicate that down-regulation of GDPGP1/mcp-1 and consequent loss of neuronal glycogen is a maladaptive response that limits neuronal stress resistance and reduces survival.

Topics: Animals; Apoptosis; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Disease Models, Animal; DNA Damage; Glucosyltransferases; Glycogen; Humans; Mice; Nerve Degeneration; Neurons

Pompe disease, caused by deficiency of acid alpha-glucosidase (GAA), leads to widespread glycogen accumulation and profound neuromuscular impairments. There has been controversy, however, regarding the role of central nervous system pathology in Pompe motor dysfunction. We hypothesized that absence of GAA protein causes progressive activation of neuropathological signaling, including pathways associated with cell death. To test this hypothesis, genomic data (Affymetrix Mouse Gene Array 2.0ST) from the midcervical spinal cord in 6 and 16 mo old Pompe (Gaa

Topics: alpha-Glucosidases; Animals; Cell Death; Cervical Vertebrae; Gene Expression Profiling; Glycogen; Glycogen Storage Disease Type II; Inflammation; Mice; Nerve Degeneration; Neurons; RNA, Messenger; Signal Transduction; Spinal Cord; Transcriptome

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.

Topics: Allosteric Regulation; alpha-Amylases; Animals; Apoptosis; Disease Progression; Dual-Specificity Phosphatases; Endoplasmic Reticulum Stress; Enzyme Activation; Gene Knockdown Techniques; Glucans; Glycogen; Glycogen Phosphorylase; Glycogen Synthase; HEK293 Cells; Hep G2 Cells; Humans; Hydrolysis; Inclusion Bodies; Lafora Disease; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Degeneration; Neurons; Phosphorylation; Protein Tyrosine Phosphatases, Non-Receptor

Glucose and glycogen are essential sources of energy for maintaining glutamate homeostasis as well as glutamatergic neurotransmission. The metabolism of glycogen, the location of which is confined to astrocytes, is affected by norepinephrine (NE), and hence, adrenergic signaling in the astrocyte might affect glutamate homeostasis with implications for excitatory neurotransmission and possibly excitotoxic neurodegeneration. In order to study this putative correlation, cultured astrocytes were incubated with 2.5 mM [U-(13)C]glucose in the presence and absence of NE as a time course for 1 h. Employing mass spectrometry, labeling in intracellular metabolites was determined. Moreover, the involvement of Ca(2+) in the noradrenergic response was studied. In unstimulated astrocytes, the labeling pattern of glutamate, aspartate, malate and citrate confirmed important roles for pyruvate carboxylation and oxidative decarboxylation in astrocytic glucose metabolism. Importantly, pyruvate carboxylation was best visualized at 10 min of incubation. The abundance and pattern of labeling in lactate and alanine indicated not only an extensive activity of malic enzyme (initial step for pyruvate recycling) but also a high degree of compartmentalization of the pyruvate pool. Stimulating with 1 μM NE had no effect on labeling patterns and glycogen metabolism, whereas 100 μM NE increased glutamate labeling and decreased labeling in alanine, the latter supposedly due to dilution from degradation of non-labeled glycogen. It is suggested that further experiments uncovering the correlation between adrenergic and glutamatergic pathways should be performed in order to gain further insight into the role of astrocytes in brain function and dysfunction, the latter including excitotoxicity.

Topics: Adrenergic Agents; Animals; Astrocytes; Calcium; Carboxy-Lyases; Citric Acid Cycle; Cytoplasm; Decarboxylation; Glucose; Glutamic Acid; Glycogen; Homeostasis; Mice; Nerve Degeneration; Norepinephrine; Oxidation-Reduction; Primary Cell Culture; Pyruvic Acid; Synaptic Transmission

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

Lafora disease (LD) is caused by mutations in either the laforin or malin gene. The hallmark of the disease is the accumulation of polyglucosan inclusions called Lafora Bodies (LBs). Malin knockout (KO) mice present polyglucosan accumulations in several brain areas, as do patients of LD. These structures are abundant in the cerebellum and hippocampus. Here, we report a large increase in glycogen synthase (GS) in these mice, in which the enzyme accumulates in LBs. Our study focused on the hippocampus where, under physiological conditions, astrocytes and parvalbumin-positive (PV(+)) interneurons expressed GS and malin. Although LBs have been described only in neurons, we found this polyglucosan accumulation in the astrocytes of the KO mice. They also had LBs in the soma and some processes of PV(+) interneurons. This phenomenon was accompanied by the progressive loss of these neuronal cells and, importantly, neurophysiological alterations potentially related to impairment of hippocampal function. Our results emphasize the relevance of the laforin-malin complex in the control of glycogen metabolism and highlight altered glycogen accumulation as a key contributor to neurodegeneration in LD.

Topics: Animals; Astrocytes; Disease Models, Animal; Female; Glycogen; Glycogen Synthase; Hippocampus; Humans; Inclusion Bodies; Lafora Disease; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Degeneration; Neurons

The dysregulation of glycogen synthase kinase-3 (GSK3) has been implicated in Alzheimer disease (AD) pathogenesis and in Abeta-induced neurotoxicity, leading us to investigate it as a therapeutic target in an intracerebroventricular Abeta infusion model. Infusion of a specific GSK3 inhibitor SB216763 (SB) reduced a downstream target, phospho-glycogen synthase 39%, and increased glycogen levels 44%, suggesting effective inhibition of enzyme activity. Compared to vehicle, Abeta increased GSK3 activity, and was associated with elevations in levels of ptau, caspase-3, the tau kinase phospho-c-jun N-terminal kinase (pJNK), neuronal DNA fragmentation, and gliosis. Co-infusion of SB corrected all responses to Abeta infusion except the induction of gliosis and behavioral deficits in the Morris water maze. Nevertheless, SB alone was associated with induction of neurodegenerative markers and behavioral deficits. These data support a role for GSK3 hyperactivation in AD pathogenesis, but emphasize the importance of developing inhibitors that do not suppress constitutive activity.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Caspase 3; Cells, Cultured; Disease Models, Animal; DNA Fragmentation; Enzyme Inhibitors; Gliosis; Glycogen; Glycogen Synthase Kinase 3; Hippocampus; Indoles; JNK Mitogen-Activated Protein Kinases; Maleimides; Maze Learning; Nerve Degeneration; Neurons; Phosphorylation; Rats; Rats, Sprague-Dawley; tau Proteins

Severe hypoglycemia constitutes a medical emergency, involving seizures, coma and death. We hypothesized that seizures, during limited substrate availability, aggravate hypoglycemia-induced brain damage. Using immature isolated, intact hippocampi and frontal neocortical blocks subjected to low glucose perfusion, we characterized hypoglycemic (neuroglycopenic) seizures in vitro during transient hypoglycemia and their effects on synaptic transmission and glycogen content. Hippocampal hypoglycemic seizures were always followed by an irreversible reduction (>60% loss) in synaptic transmission and were occasionally accompanied by spreading depression-like events. Hypoglycemic seizures occurred more frequently with decreasing "hypoglycemic" extracellular glucose concentrations. In contrast, no hypoglycemic seizures were generated in the neocortex during transient hypoglycemia, and the reduction of synaptic transmission was reversible (<60% loss). Hypoglycemic seizures in the hippocampus were abolished by NMDA and non-NMDA antagonists. The anticonvulsant, midazolam, but neither phenytoin nor valproate, also abolished hypoglycemic seizures. Non-glycolytic, oxidative substrates attenuated, but did not abolish, hypoglycemic seizure activity and were unable to support synaptic transmission, even in the presence of the adenosine (A1) antagonist, DPCPX. Complete prevention of hypoglycemic seizures always led to the maintenance of synaptic transmission. A quantitative glycogen assay demonstrated that hypoglycemic seizures, in vitro, during hypoglycemia deplete hippocampal glycogen. These data suggest that suppressing seizures during hypoglycemia may decrease subsequent neuronal damage and dysfunction.

Topics: Action Potentials; Adenosine A1 Receptor Antagonists; Animals; Anticonvulsants; Cortical Spreading Depression; Disease Models, Animal; Excitatory Amino Acid Antagonists; Glucose; Glycogen; Hippocampus; Hypoglycemia; Male; Mice; Mice, Inbred C57BL; Midazolam; Nerve Degeneration; Neurons; Receptor, Adenosine A1; Seizures; Synaptic Transmission

The present study has examined the anticonvulsant and neuroprotective effect of group II metabotropic glutamate receptor (mGluR) agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) in the model of seizures induced in immature 12-day-old rats by bilateral intracerebroventricular infusion of dl-homocysteic acid (DL-HCA, 600 nmol/side). For biochemical analyses, rat pups were sacrificed during generalized clonic-tonic seizures, approximately 45-50 min after infusion. Comparable time intervals were used for sacrificing the pups which had received 2R,4R-APDC. Low doses of 2R,4R-APDC (0.05 nmol/side) provided a pronounced anticonvulsant effect which was abolished by pretreatment with a selective group II mGluR antagonist LY341495. Generalized clonic-tonic seizures were completely suppressed and cortical energy metabolite changes which normally accompany these seizures were either normalized (decrease of glucose and glycogen) or markedly reduced (an accumulation of lactate). EEG recordings support the marked anticonvulsant effect of 2R,4R-APDC, nevertheless, this was only partial. In spite of the absence of obvious motor phenomena, isolated spikes or even short periods of partial ictal activity could be observed. Isolated spikes could also be seen in some animals after application of 2R,4R-APDC alone, reflecting most likely subclinical proconvulsant activity of this agonist. The neuroprotective effect of 2R,4R-APDC was evaluated after 24 h and 6 days of survival following DL-HCA-induced seizures. Massive neuronal degeneration, as revealed by Fluoro-Jade B staining, was observed in a number of brain regions following infusion of DL-HCA alone (seizure group), whereas 2R,4R-APDC pretreatment provided substantial neuroprotection. The present findings support the possibility that group II mGluRs are a promising target for a novel approach to treating epilepsy.

Topics: Amino Acids; Animals; Animals, Newborn; Anticonvulsants; Behavior, Animal; Brain; Brain Chemistry; Brain Injuries; Dose-Response Relationship, Drug; Drug Interactions; Electroencephalography; Excitatory Amino Acid Antagonists; Fluoresceins; Fluorescent Dyes; Functional Laterality; Glucose; Glycogen; Homocysteine; Lactic Acid; Male; Nerve Degeneration; Organic Chemicals; Proline; Rats; Rats, Wistar; Receptors, Metabotropic Glutamate; Seizures; Time Factors; Xanthenes

Hippocampal slices often have more synapses than perfusion-fixed hippocampus, but the cause of this synaptogenesis is unclear. Ultrastructural evidence for synaptogenic triggers during slice preparation was investigated in 21-day-old rats. Slices chopped under warm or chilled conditions and fixed after 0, 5, 25, 60, or 180 minutes of incubation in an interface chamber were compared with hippocampi fixed by perfusion or by immersion of the whole hippocampus. There was no significant synaptogenesis in these slices compared with perfusion-fixed hippocampus, but there were other structural changes during slice preparation and recovery in vitro. Whole hippocampus and slices prepared under warm conditions exhibited an increase in axonal coated vesicles, suggesting widespread neurotransmitter release. Glycogen granules were depleted from astrocytes and neurons in 0-min slices, began to reappear by 1 hour, and had fully recovered by 3 hours. Dendritic microtubules were initially disassembled in slices, but reassembled into normal axial arrays after 5 minutes. Microtubules were short at 5 minutes (12.3 +/- 1.1 microm) but had recovered normal lengths by 3 hours (84.6 +/- 20.0 microm) compared with perfusion-fixed hippocampus (91 +/- 22 microm). Microtubules appeared transiently in 15 +/- 3% and 9 +/- 4% of dendritic spines 5 and 25 minutes after incubation, respectively. Spine microtubules were absent from perfusion-fixed hippocampus and 3-hour slices. Ice-cold dissection and vibratomy in media that blocked activity initially produced less glycogen loss, coated vesicles, and microtubule disassembly. Submersing these slices in normal oxygenated media at 34 degrees C led to glycogen depletion, as well as increased coated vesicles and microtubule disassembly within 1 minute.

Topics: Animals; Culture Media; Dendrites; Dissection; Glycogen; Hippocampus; Hypoxia-Ischemia, Brain; Interneurons; Male; Microscopy, Electron; Microtomy; Microtubules; Nerve Degeneration; Neuroglia; Neuronal Plasticity; Neurons; Organ Culture Techniques; Oxygen; Postmortem Changes; Presynaptic Terminals; Rats; Rats, Long-Evans; Tissue Fixation

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

To answer the crucial question regarding reversibility of diabetic somatic neuropathy by whole-pancreas transplantation, metabolic studies and electron microscopic morphometry of the sciatic and testicular nerves were performed monthly for 2 years in three groups of highly inbred rats: (1) NC, 47 nondiabetic controls; (2) DC, 90 untreated alloxan-induced diabetic controls; and (3) DT, 230 diabetic rats given syngeneic pancreaticoduodenal transplants 6, 9, 12, 15, 18, and 21 months after induction of diabetes mellitus (DM). Six diabetic nerve lesions were quantitated by a "blind" protocol: (1) loss of myelinated axons, (2) intraaxonal glycogen deposits, (3) axons with glycogen deposits, (4) demyelinated axons, (5) degenerating axons, and (6) loss of intact axoglial junctions in paranodal terminal myelin loops. In the DT group, testicular nerve specimens were obtained just before transplantation and at death so that each animal served as its own control. As we have observed previously in untreated diabetic controls, all six nerve lesions progressed relentlessly for 2 years, in contrast to nondiabetic controls (p less than 0.01). Whole-pancreas transplants produced complete metabolic control of DM for life and reversed all six lesions in both sciatic and testicular nerves, even when done late in the course of DM. There was complete reversal of the nerve lesions when pancreatic transplantation was done within 15 months of the onset of DM. These results provide the first demonstration of reversal of diabetic somatic neuropathy by any form of DM therapy and extend our previous work in which whole-pancreas transplants were found to prevent both diabetic neuropathy and nephropathy and reverse mesangial enlargement in the kidney.

Topics: Animals; Axons; Blood Glucose; Diabetic Neuropathies; Glycogen; Insulin; Male; Microscopy, Electron; Nerve Degeneration; Nervous System; Osmolar Concentration; Pancreas Transplantation; Rats; Rats, Inbred Lew; Sciatic Nerve; Testis

The ultrastructure of the iris muscles and innervating nerves in patients with diabetes mellitus and approximately age-matched controls was examined by electron-microscopy. The specimens were obtained during cataract surgery. There were definite histopathological alterations at the nerve terminal innervating the dilator muscle, e.g. the presence of mitochondrial abnormalities, dense bodies and lamellar structures. No change was noted at the nerve terminal to the sphincter muscle. Moderate involvement of the muscle, especially at the sphincter, was observed in the specimens of diabetics. The control specimens had no change at the nerve terminals, while moderate change was observed at the sphincter muscle. Therefore, the change in the sphincter seen in the specimens of diabetics seemed to be mainly the result of the aging process, though the existence of early sympathetic neuropathy was confirmed.

Topics: Aged; Axons; Cataract Extraction; Cytoplasmic Granules; Diabetic Neuropathies; Glycogen; Humans; Iris; Microscopy, Electron; Middle Aged; Mitochondria, Muscle; Muscle, Smooth; Nerve Degeneration; Reflex, Pupillary

The character of glycogen metabolism disorders has been studied in the cranial cervical ganglion of the cat sympathetic trunk after the latter has been cut 1.5 cm caudally the ganglion. As the innervational connections are establishing, the glycogen metabolism is normalizing, but even after 2 months the initial level is not restored. Glycogen is proved to be one of the most sensitive tests to the lesion. In various time after cutting, the glycogen metabolism has certain specific peculiarities both in the neural cell bodies, and in the synapses. The wavy character of the glycogen-synthesizing process in the neural elements is demonstrated, with anaerobic glycolysis taking a large part in it. Certain connections with the higher centers are necessary not only for glycogen metabolism as energy resources, but to ensure a regular synthesis, particularly that of enzymes, in the neurons and synapses. The peculiarities of glycogen-synthesizing properties in the synaptic formations, after the connection with the center is broken, are closely connected with the notion on autonomity in the synaptic structures activity.

Topics: Animals; Cats; Free Radicals; Ganglia, Sympathetic; Glycogen; Histocytochemistry; Nerve Degeneration; Nerve Regeneration; Synapses; Time Factors

Topics: Animals; Brain; Epinephrine; Facial Nerve; Female; Fixatives; Glycogen; Histological Techniques; Iodoacetates; Iodoacetic Acid; Male; Nerve Degeneration; Neural Pathways; Neurons; Rabbits

Topics: Animals; Axons; Glycogen; Microscopy, Electron; Mitochondria; Mitochondrial Swelling; Nerve Degeneration; Phrenic Nerve; Ranvier's Nodes; Rats; Time Factors; Wallerian Degeneration

Ultrastructural observations have been made on the tibial and plantar nerves of Wistar rats aged 18-24 months. Changes indicative of segmental demyelination and remyelination and axonal degeneration and regeneration were prominent in the plantar nerves. Both in the plantar and tibial nerves, but particularly in the former, axonal abnormalities were frequent. These included the occurrence of multiple intra-axonal vacuoles containing glycogen and polyglucosan bodies. Axonal sequestration by adaxonal Schwann cell processes was also increased. The Schwann cell cytoplasm in relation to this activity contained bundles of filaments with the ultrastructural features of Hirano bodies. The changes in the plantar nerves probably indicate a pressure neuropathy, but the possibility of a superimposed distal axonal degeneration related to aging cannot be excluded on the present evidence. Such changes must be taken into consideration in experimental studies performed on rats of this age.

Topics: Aging; Animals; Axons; Glycogen; Male; Microscopy, Electron; Nerve Degeneration; Nerve Regeneration; Peripheral Nerves; Rats; Schwann Cells; Tibial Nerve; Vacuoles

Hyperbilirubinemia is a recognized etiologic factor in motor and hearing disorders associated with cerebral palsy. Its role in more subtle forms of neurological impairment is more controversial. Using a mutant animal model, which develops symptoms and signs closely resembling the human kernicterus syndrome, neurons of hippocampus, cerebral cortex, cochlear nuclei, losuc ceruleus, and olfactory bulb were examined by electron microscopy. Pathological changes, observed in all areas studied, consisted of mitochondrial and endoplasmic enlargement and vacuolation, with glycogen deposition; increased extracellular space; myelin figures; and degenerating changes in nerve terminals. If we make the assumption that pathologic changes in the human infant with neonatal jaundice are similar to changes in the animal model, then the widespread involvement of CNS neurons in all cortical areas examined may well help to explain the syndromes of minimal cerebral dysfunction reported in clinical studies.

Topics: Age Factors; Animals; Attention Deficit Disorder with Hyperactivity; Brain; Cerebral Cortex; Cochlear Nerve; Extracellular Space; Glycogen; Hippocampus; Humans; Hyperbilirubinemia; Locus Coeruleus; Mitochondria; Nerve Degeneration; Nerve Endings; Neurons; Olfactory Bulb; Rats

6-Hydroxydopamine (6-OH-DA) has been shown to produce degenerative changes in noradrenergic nerve terminals and preterminals in the CNS following intracisternal, intraventricular or direct injection into the brain parenchyma. Systemic injection of 6-OH-DA is known to result in degenerative changes in noradrenergic terminals in the peripheral nervous system. However, only a few studies have been carried out on the effects of systemic injections of 6-OH-DA on noradrenergic terminals in the CNS. In the present study cynomolgus and squirrel monkeys were injected intravenously on two successive days with total doses of 350 mg/kg and 150 mg/kg of 6-OH-DA, respectively, and sacrificed at 2 and 24 h following the second injection. Degenerative changes in the area postrema (AP) neurons in all injected animals were characterized by a generalized increase in electron density of cytoplasmic elements in axonal terminals and preterminals. Multilamellar bodies, clusters of clear and dense core vesicles, increased numbers of secondary lysosomes, and an increase in the number of glycogen increased markedly in injected animals, but no other glial alterations were observed. The number of mast cells in the AP was greater in injected than in noninjected animals, both in the perivascular spaces (PVS) and in parenchymal locations. Cell processes in the PVS were occasionally observed to contain electron dense bodies, and degenerative changes were seen in supraependymal processes in some injected animals.

Topics: Animals; Astrocytes; Axons; Brain; Cerebral Ventricles; Female; Glycogen; Haplorhini; Hydroxydopamines; Lysosomes; Macaca fascicularis; Mast Cells; Microscopy, Electron; Nerve Degeneration; Nerve Endings; Neurons; Norepinephrine; Saimiri

Quantative histochemical analysis of nerve degeneration in rats from zero to 192 hours was studied utilizing both Schiff reagent and PAS reaction. In addition, amylase digestion prior to PAS staining and aniline blockade of Schiff reactivity were employed. The staining intensity of all the reaction was measured histophotometrically and the mean optical density (OD) was determined for the following time intervals: 0, 24, 48, 96, and 192 hours.

Topics: Amylases; Aniline Compounds; Animals; Glycogen; Nerve Degeneration; Periodic Acid-Schiff Reaction; Rats; Schiff Bases; Sciatic Nerve; Staining and Labeling

Facial nerve neurectomy were performed in the baboon (Papio papio). Histochemical investigations showed usual criteria of such lesions. Therefore a loose of glycogene within the Type I muscular fibers was observed in animals with a former facial spasm.

Topics: Adenosine Triphosphatases; Animals; Atrophy; Facial Muscles; Facial Nerve; Glycogen; Haplorhini; Necrosis; Nerve Degeneration; Papio; Photic Stimulation; Spasm

Topics: 1,4-alpha-Glucan Branching Enzyme; Adenine Nucleotides; Adrenal Cortex Hormones; Animals; Blood Glucose; Body Temperature Regulation; Brain; Brain Diseases; Brain Injuries; Catecholamines; Central Nervous System; Chemical Phenomena; Chemistry, Physical; Glycogen; Glycogen Synthase; Histocytochemistry; Histological Techniques; Humans; Hypoxia, Brain; Insulin; Ischemia; Nerve Degeneration; Phenobarbital; Phosphorylases; Radiation Effects; Radiation, Ionizing; Rats; Retina

The authors describe in biopsies from 6 cases of Werdnig-Hoffmann disease, including 2 of the more benign type, the ultrastructural typical aspects of denervation. They compare their findings with those of other workers. The striking points are the great variation in the diameter of the muscle fibres and the myofibrils, the disorganisation of the myofibrils, the sarcomeres and the filaments, with persistance of the relations between thick and thin filaments at various levels, the modifications of the Z-band and the triads in chains. The folds and the basement membrane are examined. Centrioles are present in a muscle fibre and in a satellite. Glycogen is very abundant. The nerves seem normal but some Schwann cells contain pi granules which are not observed usually at the age of the patient. The end plates and a muscle spindle are normal.

Topics: Basement Membrane; Cell Membrane; Child, Preschool; Cytoplasmic Granules; Demyelinating Diseases; Female; Glycogen; Humans; Infant; Male; Motor Endplate; Motor Neurons; Muscles; Muscular Atrophy; Myofibrils; Nerve Degeneration; Peripheral Nerves; Sarcoplasmic Reticulum; Syndrome

The material, with few exceptions, consists of PAS-gallocyanin stained paraffin sections from 4- to 6-month-old male rabbits fixed by perfusion first with saline and then with Bouin's solution. (1) In animals treated with cortisone prior to and subsequent to axotomy, the neurons exhibit an accelerated dispersal and delayed reconstitution of Nissl substance (ribosomes). While mitotic activity is depressed at various sites, formation of new microglial cells is evident. Neuronal degeneration with karyorrhexis is occasionally noted in single neurons in the lateral parts of the facial nucleus. An increase in intraneuronal glycogen deposition is manifested by a greater number of glycogen-rich neurons; such neurons are depleted of their glycogen after axotomy. (2) In other animals, reoperation of the facial nerve on the 6th, 22nd, 60th and 120th day, followed by survival of 3 days, results in dispersal of restored Nissl substance and in increased extravascular mitotic activity which is of less intensity than in single-operated animals.

Topics: Animals; Axons; Cortisone; Facial Nerve; Glycogen; Male; Mitosis; Nerve Degeneration; Neuroglia; Neurons; Rabbits; Retrograde Degeneration

A chromatolysis study, 14 to 21 days following denervation, showed the spinal cord representation of the nerve to the posterior latissimus dorsi muscle to be in the ventrolateral cell column between cervical ganglia 14 and 15. to characterize cevical neruos nt undergoing chromatolysis, histochemical stuies were done the cords of additional nondenervated animals. Staining reactions for beta-hydrocybutyrate dehydrogenase, succinic dehydrogenase and cholinesterase did not reveal any quantitative differences between motor neurons in cervical segments 14 and 15 of normal and dystrophic birds. Motor neurons are positive for beta-hydroxybutyrate dehydrogenase and succinic dehydrogenase, but the surrounding neuropil is positive for the latter only. No pseudocholinesterase activity is found in the ventral horn cells, but true cholinesterase is present in most of the neurons...

Topics: Animals; Chickens; Cholinesterases; Glycogen; Histocytochemistry; Hydroxybutyrate Dehydrogenase; Motor Endplate; Motor Neurons; Muscle Denervation; Muscles; Muscular Dystrophy, Animal; Nerve Degeneration; Spinal Cord; Succinate Dehydrogenase

Topics: Animals; Animals, Newborn; Cell Nucleus; Cytoplasm; Cytoplasmic Granules; Endoplasmic Reticulum; Glycogen; Heterochromatin; Inclusion Bodies; Microscopy, Electron; Mitochondria; Nerve Degeneration; Neuroglia; Rabbits; Rats; Ribosomes; Spinal Cord; Thalamic Nuclei

Topics: Animals; Cell Differentiation; Cell Nucleus; Cytoplasmic Granules; Endoplasmic Reticulum; Extracellular Space; Glycogen; Golgi Apparatus; Hydra; Inclusion Bodies; Lysosomes; Microscopy, Electron; Microtubules; Mitochondria; Nerve Degeneration; Nerve Regeneration; Nervous System; Nervous System Physiological Phenomena; Neurons; Neurosecretion; Ribosomes; Time Factors

Topics: Animals; Axons; Carotid Body; Cats; Cytoplasmic Granules; Ganglia, Autonomic; Glossopharyngeal Nerve; Glycogen; Microscopy, Electron; Microtubules; Models, Neurological; Nerve Degeneration; Nerve Endings; Vagus Nerve

Topics: Animals; Axons; Chronic Disease; Dendrites; Edema; Extracellular Space; Glycogen; Hemorrhage; Macrophages; Microscopy, Electron; Microscopy, Fluorescence; Nerve Degeneration; Pressure; Rabbits; Spinal Cord Injuries; Time Factors

Topics: Animals; Anura; Axons; Cell Nucleus; Collagen; Connective Tissue Cells; Cytoplasmic Granules; Electrophysiology; Endoplasmic Reticulum; Glycogen; Glycosaminoglycans; Inclusion Bodies; Microscopy, Electron; Microtubules; Myelin Sheath; Nerve Degeneration; Nerve Fibers, Myelinated; Neurophysiology; Pineal Gland; Rana esculenta; Time Factors

Topics: Animals; Brain Stem; Cats; Cerebral Cortex; Glycogen; Hyperplasia; Inferior Colliculi; Microscopy, Electron; Myelin Sheath; Nerve Degeneration; Neural Pathways; Neurofibrils; Synapses; Synaptic Vesicles; Time Factors

Topics: Animals; Axons; Cytoplasm; Cytoplasmic Granules; Dendrites; Glycogen; Mitochondria; Nerve Degeneration; Nerve Endings; Ocular Physiological Phenomena; Superior Colliculi; Synaptic Vesicles; Turtles; Visual Pathways

Topics: Animals; Demyelinating Diseases; Glycogen; Microscopy, Electron; Myelin Sheath; Nerve Crush; Nerve Degeneration; Nerve Fibers, Myelinated; Neuroglia; Rats; Spinal Cord Injuries; Spinal Nerve Roots; Synaptic Vesicles

Topics: Animals; Blood Proteins; Cerebral Cortex; Cytoplasmic Granules; Edema; Encephalomalacia; Endothelium; Extracellular Space; Glycogen; Golgi Apparatus; Histocytochemistry; Inflammation; Microscopy, Electron; Mitochondria; Nerve Degeneration; Neuroglia; Neurons; Nissl Bodies; Ribosomes; Sheep; Sheep Diseases; Thiamine

Topics: Animals; Axons; Endoplasmic Reticulum; Glycogen; Golgi Apparatus; Male; Microscopy, Electron; Mitochondria; Motor Neurons; Nerve Degeneration; Rats; Ribosomes; Synapses; Trigeminal Nerve

Topics: Abnormalities, Multiple; Age Determination by Skeleton; Bone and Bones; Consanguinity; Developmental Disabilities; Female; Foot; Glycogen; Growth Disorders; Hand; Humans; Infant; Intellectual Disability; Male; Microscopy, Electron; Muscles; Muscular Atrophy; Myofibrils; Nerve Degeneration; Pedigree; Rubinstein-Taybi Syndrome; Sarcoplasmic Reticulum

Topics: Animals; Axons; Cytoplasmic Granules; Glycogen; Inclusion Bodies; Microscopy, Electron; Microtubules; Mitochondria; Myelin Sheath; Nerve Degeneration; Nerve Regeneration; Organoids; Rats; Schwann Cells; Sciatic Nerve; Time Factors

Topics: Acute Disease; Adolescent; Adult; Biopsy; Cytoplasm; Demyelinating Diseases; Female; Glycogen; Hodgkin Disease; Humans; Leukemia; Male; Microscopy; Microscopy, Electron; Middle Aged; Nerve Degeneration; Polyneuropathies; Schwann Cells; Sural Nerve; Vinblastine; Vinca Alkaloids; Vincristine

Topics: Animals; Blood Vessels; Cell Nucleus; Cytoplasm; Glycogen; Male; Mesencephalon; Microscopy, Electron; Nerve Degeneration; Neuroglia; Neurons; Nissl Bodies; Rats; Ribosomes; Trigeminal Nerve

Topics: Amino Acids; Brain Chemistry; Brain Diseases; Cerebellum; Cerebral Cortex; Cerebrosides; Cholesterol; Electroencephalography; Glycogen; Growth Disorders; Hair; Humans; Infant; Male; Nerve Degeneration; Pedigree; Phenobarbital; Phenytoin; Phospholipids; Plasmalogens; Seizures; Ubiquinone; Vitamin E

Topics: Animals; Cytoplasmic Granules; Dendrites; Endoplasmic Reticulum; Glycogen; Microscopy, Electron; Nerve Degeneration; Neurons; Rats; Reflex, Monosynaptic; Spinal Cord; Spinal Nerve Roots; Staining and Labeling; Synapses; Synaptic Vesicles

Topics: Adult; Aged; Axons; Cerebral Cortex; Dementia; Glycogen; Hippocampus; Humans; Inclusion Bodies; Microscopy, Electron; Middle Aged; Mitochondria; Nerve Degeneration; Neurofibrils; Neuroglia; Neurons; Nissl Bodies

Topics: Animals; Female; Glucosephosphate Dehydrogenase; Glucosyltransferases; Glycogen; Male; Motor Neurons; Nerve Degeneration; Nissl Bodies; Rabbits; Spinal Cord

Topics: Animals; Axons; Cell Survival; Cytoplasm; Cytoplasmic Granules; Endoplasmic Reticulum; Glycogen; Limbic System; Macrophages; Meninges; Microscopy, Electron; Microtubules; Nerve Degeneration; Olfactory Nerve; Rabbits; Ribosomes; Time Factors

Topics: Adult; Aphonia; Child; Child, Preschool; Chronaxy; Citric Acid Cycle; Demyelinating Diseases; Energy Metabolism; Female; Glycogen; Histocytochemistry; Humans; Infant; Leukodystrophy, Metachromatic; Male; Middle Aged; Muscles; Muscular Atrophy; Nerve Degeneration; Syndrome

Topics: Animals; Axons; Cytoplasm; Demyelinating Diseases; Glycogen; Goats; Histocytochemistry; Microscopy, Electron; Mitochondrial Swelling; Nerve Degeneration; Nerve Tissue; Neurons; Peripheral Nerves; Peripheral Nervous System Diseases; Plant Poisoning; Schwann Cells; Sciatic Nerve; Time Factors

Topics: Animals; Axons; Glycogen; Microtubules; Nerve Degeneration; Olfactory Nerve; Rabbits

Topics: Animals; Cell Membrane; Choroid; Fundus Oculi; Glycogen; Macula Lutea; Microscopy, Electron; Nerve Degeneration; Oxygen; Rabbits; Regional Blood Flow; Retina; Sensory Receptor Cells; Synapses; Time Factors; Vitamin E

Topics: Cell Membrane; Cerebellar Neoplasms; Cytosol; Glycogen; Humans; Microscopy, Electron; Mitochondria; Nerve Degeneration; Neurilemmoma; Neurofibrils; Reticular Formation; Spinal Cord Neoplasms

Topics: Amyotrophic Lateral Sclerosis; Glycogen; Humans; Microscopy, Electron; Mitochondria, Muscle; Muscles; Myofibrils; Myotonic Dystrophy; Nerve Degeneration; Spinal Cord Diseases

Topics: Animals; Brain Diseases; Cerebral Cortex; Cobalt; Dendrites; Glycogen; Histocytochemistry; Microscopy, Electron; Necrosis; Nerve Degeneration; Neuroglia; Rats

Topics: Animals; Animals, Newborn; Cerebellum; Culture Techniques; Cytoplasmic Granules; Demyelinating Diseases; Glycogen; Histocytochemistry; Immune Sera; Microscopy; Microscopy, Electron; Multiple Sclerosis; Myelin Sheath; Nerve Degeneration; Neuroglia; Rats

Topics: Animals; Cats; Glycogen; Hypothalamus; Nerve Degeneration; Peripheral Nerve Injuries; Sciatic Nerve; Wounds and Injuries

Topics: Alcoholism; Animals; Cardiomyopathy, Alcoholic; Electrons; Endoplasmic Reticulum; Glycogen; Heart Diseases; Humans; Lipids; Lysosomes; Microscopy; Microscopy, Electron; Mitochondria; Myocardium; Myofibrils; Nerve Degeneration; Pathology

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Axons; Carbohydrate Metabolism; Fructose; Glucose; Glycogen; Hypoxia; In Vitro Techniques; Ischemia; Lactates; Nerve Degeneration; Nervous System Diseases; Neurilemma; Oxygen Consumption; Peripheral Nerves; Phosphates; Phosphocreatine; Rabbits; Schwann Cells