Morphology and histochemistry of Wilsonian and hepatogenic gliopathy in tissue culture

Mj, Mossakowski; Renkawek, K; Kraśnicka, Z; Smialek, Maciej Jerzy; Pronaszko, A

doi:10.1007/bf00686958

Cited by 24 publications

(5 citation statements)

References 17 publications

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“…These correspond to the Alzheimer Type II cells, resulting in CNS dysfunction (Norenberg, 1981). Mossakowski et al (1970) and Gregorios et al (1985) found these cells in mixed glial-neuronal and glial cultures, respectively, exposed to excess ammonia. Hyperammonemia resulting from a PCS is accompanied by neurological symptoms and brain morphological changes in rats (Norenberg et al, 1974;Butterworth and Giguere, 1984).…”

Section: Discussionmentioning

confidence: 99%

The action of ammonia on astrocyte glycogen and glycogenolysis

Dombro

Hutson

Norenberg

1993

Molecular and Chemical Neuropathology

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Most of the brain glycogen, a major energy reserve that can be mobilized in response to increased neuronal activity, resides in the astrocyte, the site of the neuropathological abnormality found in hepatic encephalopathy (HE). Ammonia, a neurotoxin implicated in the pathogenesis of HE, has been reported to cause a depletion of glycogen in primary astrocyte cultures. To further investigate the action of ammonia on glycogen levels, cultured astrocytes were exposed to ammonium chloride (1-5 mM) for various times up to 7 d. Treatment with ammonia for 24 h did not alter deoxyglucose uptake, but significantly lowered peak glycogen values (found at 1.5 h following feeding with medium containing 5.5 mM glucose) in a concentration-dependent manner. This inhibitory effect was not observed after longer exposure times to ammonia. Three day treatment of cells did, however, significantly reduce norepinephrine-stimulated glycogenolysis, an effect not seen after 1 d of ammonia treatment. Part of the neurotoxic action of long term ammonia exposure in humans and experimental animals may be to inhibit the breakdown of glycogen. The effect of ammonia on astrocyte glycogen synthesis and/or breakdown may disrupt glial neuronal signaling and thus play a role in the pathogenesis of HE.

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Section: Discussionmentioning

confidence: 99%

The action of ammonia on astrocyte glycogen and glycogenolysis

Dombro

Hutson

Norenberg

1993

Molecular and Chemical Neuropathology

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“…Liver cirrhosis results in chronic hyperam monemia and in increased brain ammonia concentra tions. Blood ammonia concentrations are increased in experimental PSE in both rats [4] and dogs [5], Alzheimer type II astrocytes have been described in the brains of patients with congenital hyperammonemic syn dromes resulting from inherited disorders of urea cycle enzymes [6] as well as in the brains of experimental ani mals with urease-induced hyperammonemia [7], Fur thermore, exposure o f cultured astrocytes to the serum of patients in hepatic coma results in Alzheimer type II changes [8], and exposure of cultured astrocytes to am monia in concentrations similar to those observed in the brains of animals with experimental hepatic coma like wise results in Alzheimer type II changes [9].…”

Section: Neuropathology Of Psementioning

confidence: 99%

Portal-Systemic Encephalopathy: A Disorder of Neuron-Astrocytic Metabolic Trafficking

Butterworth

1993

Dev Neurosci

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Portal-systemic encephalopathy (PSE) is a major neuropsychiatry complication of chronic liver disease. Neuropathologic evaluation of brain tissue from cirrhotic patients who died in hepatic coma reveals astrocytic (rather than neuronal) changes referred to as Alzheimer type II astrocytosis. Evidence to date suggests that Alzheimer type II astrocytosis is the result of ammonia neurotoxicity. Exposure of cultured astrocytes to concentrations of ammonia equivalent to those encountered in brain in experimental PSE results in Alzheimer type II astrocytosis as well as changes in other astrocytic parameters such as glial fibrillary acidic protein and glycogen metabolism. A second characteristic of PSE is the appearance of increased densities of ''peripheral-type'' benzodiazepine receptors (PTBRs) in both brain and peripheral tissues. In brain, PTBRs are highly localized on astrocytic outer mitochondrial membranes. Experimental PSE resulting from portacaval anastomosis in the rat results in increased densities of PTBRs in brain and in increased expression of the endogenous PTBR ligand octadecaneuropeptide in nonneuronal elements. It is suggested that the PTBR and its endogenous ligands could mediate the astrocytic response to chronic exposure to ammonia in PSE. Astrocytic changes in PSE are accompanied by disruption of neuron-astrocytic metabolic trafficking. In particular, reuptake of the neurotransmitter glutamate into the perineuronal astrocyte is inhibited in PSE resulting in glutamatergic synaptic dysregulation and potentially compromised astrocytic energy metabolism. Astrocytic metabolism of monoamine neurotransmitters may also be increased as a result of increased activities of monoamine oxidase MAO_B.

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“…Three groups of cultures were studied, beginning at 14 DIV, i) controls (triangles), ii) treated with 7 mM ammonia alone (open circles), and iii) exposed to 7 mM ammonia plus 0.5 mM dBcAMP (filled circles). of lysosomal enzymes such as acid phosphatase (Mossakowski et al, 1970) and cathepsin D (Fig. 9J-L) increases.…”

Section: Discussion Cultured Muller Cells Are Sensitive To Enhanced Amentioning

confidence: 97%

“…These astroglial alterations consist of an enlarged nucleus (for quantitative measures, see Martin et al, 1989a,b), a change in the expression of intermediate filament proteins, accumulation of cellular debris, and a series of metabolic changes. They can also be produced in astroglial cell cultures, by enhancement of the ammonia concentration in the bathing medium (Gregorios et al, 1985a,b;Mossakowski et al, 1970;Noren-0 1995 Wiley-Liss, Inc. berg et al, 1990b). In the course of such experiments it was discovered that application of dibutyryl-cyclic adenosine monophosphate (dBcAMP) exerts a protective effect against the exposure to ammonia (Gregorios et al, 1986;Norenberg et al, 1990a).…”

Section: Introductionmentioning

confidence: 97%

“…These astroglial alterations consist of an enlarged nucleus (for quantitative measures, see Martin et al, 1989a,b), a change in the expression of intermediate filament proteins, accumulation of cellular debris, and a series of metabolic changes. They can also be produced in astroglial cell cultures, by enhancement of the ammonia concentration in the bathing medium (Gregorios et al, 1985a,b;Mossakowski et al, 1970;Noren-man, 1986;Reichenbach and Robinson, 1995;Ripps and Witkovsky, 1985). Nevertheless, to the best of our knowledge there were no reports on any changes of the retina and its glia in cases of hepatic insufficiency, until we were recently able to demonstrate morphological and immunocytochemical alterations of Miiller cells as well as functional disturbances of the retina possibly caused by Muller cell dysfunction in human subjects suffering from hepatic failure.…”

Section: Introductionmentioning

confidence: 99%

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Effects of enhanced extracellular ammonia concentration on cultured mammalian retinal glial (müller) cells

Reichenbach

Stolzenburg

Wolburg

et al. 1995

Glia

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Müller (glial) cells of the neonatal rabbit retina were cultured as confluent monolayers and exposed to enhanced concentrations of ammonia (0.25, 0.5, 1, 3, 7, and 10 mM) in medium for various periods (30 min to 10 d). This caused, in a time- and dose-dependent manner, similar changes in the Müller cells as had previously been described in cultured astrocytes. The most conspicuous events were 1) an increasing size of cell nuclei, 2) an accumulation of phagocytotic vacuoles, and 3) a rearrangement of intermediate filaments. 4) A considerable number of cells died when higher ammonia concentrations were applied for more than 1 h. Simultaneous application of dibutyryl-cyclic adenosine monophosphate (dBcAMP) prevented almost completely both the increase in cell nucleus size and the changes of intermediate filaments, but only partly the early cell death of a subpopulation of cells, and the accumulation of phagocytotic vacuoles. Further changes evoked by enhanced ammonia concentration were 5) an accumulation of lipofuscin-like material ("fatty degeneration") revealed by lipophilic stain, 6) reduced immunoreactivity for cathepsin D, and increased immunoreactivity for 7) glial fibrillary acidic protein, 8) glutamine synthetase, and 9) bcl-2 protooncogene protein. These findings are discussed in respect to the possible underlying pathophysiological mechanisms.

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Morphology and histochemistry of Wilsonian and hepatogenic gliopathy in tissue culture

Cited by 24 publications

References 17 publications

The action of ammonia on astrocyte glycogen and glycogenolysis

The action of ammonia on astrocyte glycogen and glycogenolysis

Portal-Systemic Encephalopathy: A Disorder of Neuron-Astrocytic Metabolic Trafficking

Effects of enhanced extracellular ammonia concentration on cultured mammalian retinal glial (müller) cells

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