252 research outputs found
Interferon beta-1b in treatment-naive paediatric patients with relapsing-remitting MS: 2-year results from the BETAPAEDIC study
No full textGlycogen synthesis in the astrocyte: from glycogenin to proglycogen to glycogen
No full textThe astrocyte of the newborn rat brain has proven to be a versatile system in which to study glycogen biogenesis. We have taken advantage of the rapid stimulation of glycogen synthesis that occurs when glucose is fed to astrocytes, and the marked limitation on this synthesis that occurs in astrocytes previously exposed to ammonium ions. These observations have been related to our earlier reports of the initiation of glycogen synthesis on a protein primer, glycogenin, and the discovery of a low‐molecular‐weight form of glycogen, proglycogen. The following conclusions have been drawn: 1) In the ammonia‐treated astrocytes starved of glucose, free glycogenin is present. 2) When these astrocytes are fed with glucose, proglycogen is synthesized from the glycogenin primer by a glycogen‐synthase‐like UDPglucose transglucosylase activity (proglycogen synthase) distinct from the well‐recognized glycogen synthase, and synthesis stops at this point. 3) Proglycogen is the precursor of macromolecular glycogen, which is synthesized from proglycogen by glycogen synthase when glucose is fed to untreated astrocytes, accounting for the much greater accumulation of total glycogen. 4) The stimulus to proglycogen and macroglycogen synthesis that occurs on feeding glucose to untreated or ammonia‐treated astrocytes is the result of the activation of proglycogen synthase, not of glycogen synthase. 5) Therefore, in the synthesis of macromolecular glycogen from glycogenin via proglycogen, the step between glycogenin and proglycogen is rate‐limiting. 6) The discovery of additional potential control points in glycogen synthesis, now emerging, may assist the identification of so‐far‐unexplained aberrations of glycogen metabolism.—Lomako, J., Lomako, W. M., Whelan, W. J., Dombro, R. S., Neary, J. T., and Norenberg, M. D. Glycogen synthesis in the astrocyte: from glycogen to proglycogen to glycogen. FASEB J. 7: 1386‐1393; 1993
Åttonde fortsättningen af strödda besvarade lagfrågor. Hvilka, med den vidt lagfarne juridiska facultetens i Upsala samtycke, under Herr Professorens i Svenska och Romerska Lagfarenheten, samt Ledamotens uti Kongl. Vetenskaps Societeten härstädes, Doct. Daniel Solanders inseende, til almänt ompröfvande äro utgifne af Martinus Norenberg från Vestergöthland. Uti den större Gustavianska Lärosalen f. m. Den VI. Decemb. MDCCLXXVII. [Elektronisk resurs]
No full textDistribution of glutamine synthetase in the rat central nervous system.
No full text The results of a light microscopic immunohistochemical study of glutamine synthetase in rat nervous system are presented. In all sites studied the enzyme was confined to astrocytes. Except for trace amounts in ependymal cells, the enzyme was not observed in other cells of the nervous system including neurons, choroid plexus, third ventricular tanycytes, subependymal cells and mesodermally-derived elements. The intensity of astrocyte staining varied in different regions with the greatest degree noted in the hippocampus and cerebellar cortex while the least was noted in brain stem, deep cerebellar nuclei and spinal cord. The glutamine synthetase content correlated well with sites of suspected glutamergic activity in keeping with the view of a critical role of astrocytes in the regulation of the putative neurotransmitter glutamic acid. </jats:p
Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function
No full textThe peripheral-type benzodiazepine receptor or recognition site (PBR) is a widely distributed transmembrane protein that is located mainly in the outer mitochondrial membrane. The PBR binds to high-affinity drug ligands and cholesterol. Many functions are associated directly or indirectly with the PBR, including the regulation of cholesterol transport and the synthesis of steroid hormones, porphyrin transport and heme synthesis, apoptosis, cell proliferation, anion transport, regulation of mitochondrial functions and immunomodulation. Based on these functions, there are many potential clinical applications of PBR modulation, such as in oncologic, endocrine, neuropsychiatric and neurodegenerative diseases. Although 'PBR' is a widely used and accepted name in the scientific community, recent data regarding the structure and molecular function of this protein increasingly support renaming it to represent more accurately its subcellular role (or roles) and putative tissue-specific function (or functions). Translocator protein (18 kDa) is proposed as a new name, regardless of the subcellular localization of the protein
P2Y₂ Nucleotide Receptors Expressed Heterologously in Sympathetic Neurons Inhibit Both N-Type Ca²⁺ and M-Type K⁺ Currents
No full textThe P2Y₂ receptor is a uridine/adenosine triphosphate (UTP/ATP)-sensitive G-protein-linked nucleotide receptor that previously has been reported to stimulate the phosphoinositide signaling pathway. Messenger RNA for this receptor has been detected in brain tissue. We have investigated the coupling of the molecularly defined rat P2Y₂ receptor to neuronal N-type Ca²⁺ channels and to M-type K⁺ channels by heterologous expression in rat superior cervical sympathetic (SCG) neurons. After the injection of P2Y₂cRNA, UTP inhibited the currents carried by both types of ion channel. As previously reported [Filippov AK, Webb TE, Barnard EA, Brown DA (1997) Inhibition by heterologously expressed P2Y₂nucleotide receptors of N-type calcium currents in rat sympathetic neurones. Br J Pharmacol 121:849–851], UTP inhibited the Ca²⁺ current (I_{Ca(N)} by up to 64%, with an IC₅₀ of ∼0.5 μm. We now find that UTP also inhibited the K⁺_{M} current (I_{K(M)} by up to 61%, with an IC₅₀ of ∼1.5 μm. UTP had no effect on either current in neurons not injected with P2Y₂ cRNA. Structure–activity relations for the inhibition of I_{Ca(N)} and I_{K(M)} in P2Y₂ cRNA-injected neurons were similar, with UTP ≥ ATP > ITP ≫ GTP,UDP. However, coupling to these two channels involved different G-proteins: pretreatment withPertussis toxin (PTX) did not affect UTP-induced inhibition of I_{K(M)} but reduced inhibition of I_{Ca(N)} by ∼60% and abolished the voltage-dependent component of this inhibition. In unclamped neurons, UTP greatly facilitated depolarization-induced action potential discharges. Thus, the single P2Y₂ receptor can couple to at least two G-proteins to inhibit both Ca²⁺_{N} and K⁺_{M} channels with near-equal facility. This implies that the P2Y₂ receptor may induce a broad range of effector responses in the nervous system
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Ammonia Neurotoxicity: Role of the Mitochondrial Permeability Transition
No full textHepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with severe liver disease. Although the mechanisms responsible for HE remain elusive, ammonia is generally considered to be involved in its pathogenesis, and astrocytes are thought to be the principal target of ammonia neurotoxicity. Altered bioenergetics and oxidative stress are also thought to play a major role in this disorder. In this paper, we present data invoking the mitochondrial permeability transition (MPT) as a factor in the pathogenesis of HE/hyperammonemia. The MPT is a Ca2+-dependent, cyclosporin A (CsA) sensitive process due to the opening of a pore in the inner mitochondrial membrane that leads to a collapse of ionic gradients and ultimately to mitochondrial dysfunction. Many of the factors that facilitate the induction of the MPT are also known to be implicated in the mechanism of HE, including free radicals, Ca2+, nitric oxide, alkaline pH, and glutamine. We have recently shown that treatment of cultured astrocytes with 5 mM NH4Cl resulted in a dissipation of the mitochondrial membrane potential (ΔΨ
m
), which was sensitive to CsA. Similarly treated cultured neurons failed to show a loss of the ΔΨ
m
. Further support for the ammonia induction of the MPT was obtained by observing an increase in mitochondrial permeability to 2-deoxyglucose-6-phosphate, and a decrease in calcein fluorescence in astrocytes after ammonia treatment, both of which were also blocked by CsA. CsA was likewise capable of exerting a protective effect against hyperammonemia in mice. Taken together, our data suggest that the MPT represents an important component of the pathogenesis of HE and other hyperammonemic states
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A light and electron microscopic study of experimental portal-systemic (ammonia) encephalopathy. Progression and reversal of the disorder
No full textA sequential light and electron microscopic study of cerebral cortex was performed in a rat model of portal-systemic encephalopathy produced by creating a portacaval shunt and followed by ammoniate resin feedings. Prior to coma, astrocytes were characterized ultrastructurally by marked cytoplasmic enlargement, proliferation of mitochondria and endoplasmic reticulum, and an accumulation of cytoplasmic glycogen. The Alzheimer type II astrocyte change was seen only in coma and was characterized ultrastructurally by additional hydropic and degenerative mitochondrial and nuclear changes. Attempts at reversal of the encephalopathy were successful only if ammoniated resin feedings were discontinued prior to coma. Results suggest (1) that the astrocyte response initially reflects an ammonia-induced increased metabolic activity in that cell; (2) that subsequently a gliopathy develops having the light microscopic appearance of the Alzheimer type II change; and (3) that the Alzheimer type II astrocyte change may be responsible for an irreversible clinical course in this experimental condition
A light and electron microscopic study of experimental portal-systemic (ammonia) encephalopathy. Progression and reversal of the disorder
No full textA sequential light and electron microscopic study of cerebral cortex was performed in a rat model of portal-systemic encephalopathy produced by creating a portacaval shunt and followed by ammoniate resin feedings. Prior to coma, astrocytes were characterized ultrastructurally by marked cytoplasmic enlargement, proliferation of mitochondria and endoplasmic reticulum, and an accumulation of cytoplasmic glycogen. The Alzheimer type II astrocyte change was seen only in coma and was characterized ultrastructurally by additional hydropic and degenerative mitochondrial and nuclear changes. Attempts at reversal of the encephalopathy were successful only if ammoniated resin feedings were discontinued prior to coma. Results suggest (1) that the astrocyte response initially reflects an ammonia-induced increased metabolic activity in that cell; (2) that subsequently a gliopathy develops having the light microscopic appearance of the Alzheimer type II change; and (3) that the Alzheimer type II astrocyte change may be responsible for an irreversible clinical course in this experimental condition
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