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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 47 (1986), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have examined if the age-related susceptibility of DBA/2J mice to audiogenic seizures is the result of an abnormality in the number or sensitivity of brain adrenoceptors. The binding of α1--, α2--, and β-adrenoceptor ligands to membranes prepared from whole brain or regions of brain of DBA/2J mice was measured at various ages, corresponding to the periods before, during, and after the maximal sensitivity to audiogenic seizures. For comparison, we have studied concurrently age-matched C57 B1/6 mice, a strain resistant to audiogenic seizures at all ages. There was no difference in the binding of α2-- or β-adrenoceptor ligands to whole brain membranes between the two strains of mice at any age. The maximal number of α1--adrenoceptor binding sites was lower in whole brains of DBA/2J mice than of C57 B1/6 mice at all ages studied except 13–15 days of age. The differences were small (maximally 17%) but were statistically significant at 21–23 days of age, the time of maximal sensitivity of DBA/2J mice to audiogenic seizures. No difference between the two strains was found in the number or affinity of α1-- or α2--adrenoceptor binding sites at any age in any of the brain regions studied. The age-related susceptibility of DBA/2J mice to audiogenic seizures is not the result of an abnormality in number or sensitivity of α2-- or β-adrenoceptor binding sites, but a reduced number of α1--adrenoceptor binding sites may be involved.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 39 (1982), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The properties of γ-aminobutyric acid recognition sites, benzodiazepine binding sites and the effect of exogeneous γ-aminobutyric acid on benzodiazepine binding were determined in crude membrane fractions prepared from the brains of DBN/2 mice at ages before (8-9 and 17-18 days), during (22-23 and 28-29 days) and after (40-43 days) the age of high susceptibility to audiogenic seizures. These have been compared with data from age- matched mice of a strain (TO) with lower audiogenic seizure susceptibility. The number of high-affinity [3H]γ-aminobutyric acid binding sites was lower at all ages in DBN/2 mice compared with TO mice, but the affinity was higher in DBN/2 mice. The number of low-affinity [3H]y-aminobutyric acid binding sites was lower at 8-9 days and 40-43 days in DBN/2 mice, but was not significantly different from TO mice at other ages. For [3H]flunitrazepam binding, the only difference found was a slight reduction in the number of binding sites at 28-29 days of age in DBN/2 mice. γ-Aminobutyric acid stimulation of [3H]-flunitrazepam binding was not significantly different up to 22-23 days of age, but was higher in DBN/2 mice at 28-29 days and lower at 40-43 days. Impairment of γ-aminobutyric acid function is a possible permissive factor in the age-dependent audiogenic seizure susceptibility in DBN/2 mice.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 39 (1982), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: DBA/2 mice between 21 and 28 days of age are highly susceptible to sound-induced seizures. Drug studies suggest a possible deficit of γ-Aminobutyric acid (GABA)-mediated neurotransmission may be involved. We have measured the whole brain GABA concentration and glutamic acid decar-boxylase activity in DBA/2 mice at various ages before, during, and after the period of maximal susceptibility to audiogenic seizures. Corresponding determinations were carried out on age-matched TO mice, a strain much less susceptible to audiogenic seizures than DBA/2 mice at all ages. No significant differences in GABA concentration or glutamic acid decarboxylase activity were found between strains at any age. The susceptibility of DBA/2 mice to audiogenic seizures does not result from a gross inability to synthesise or store GABA.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 24 (1975), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: —The convulsant action of methyldithiocarbazinate (MDTC), thiocarbohydrazide (TCH) and thiosemicarbazide (TSC) has been studied in mice. The relationship between dose and time to convulsions indicated that MDTC has a dual action and is more potent than TSC. Pretreatment of mice with pyridoxal phosphate (0.25 mmol/kg) protected against convulsions and death produced by low doses of MDTC or TCH, and low or high doses of TSC. Pretreatment with pyridoxine hydrochloride (0.25 mmol/kg) protected mice against TSC but not against TCH. It protected against low doses of MDTC (0.12 mmol/kg), but shortened the latency to convulsions after intermediate doses of MDTC (0.37 mmol/kg).Glutamate decarboxylase activity (GAD, EC 4.1.1.15) in whole brain homogenates from mice killed at the onset of seizures, was significantly reduced by all 3 drugs at all doses. This inhibition did not exceed 30% after any dose of TSC or TCH, but was 64% in mice killed 4 min after the injection of MDTC (0.98 mmol/kg). The addition of pyridoxal phosphate to brain homogenates abolished GAD inhibition after MDTC but not after TCH. In vitro brain GAD was 50% inhibited by 10−4m-MDTC, 18% by 10−4m-TSC and 8% by 10 −4m-TCH. Kinetic studies suggested that at low concentrations MDTC inhibits by competing with pyridoxal phosphate. At the onset of convulsions the cerebral content of pyridoxal phosphate was reduced after low or high doses of TSC (0.27 and 2.2 mmol/kg) and after high doses of MDTC (0.98 mmol/kg). All three drugs (at 10−5−10−4m) inhibited pyridoxal phosphokinase (EC 2.7.1.35) in vitro. Short latency convulsions after MDTC (0.37–0.98 mmol/kg) very probably arise from inhibition of cerebral GAD, due to competition for coenzymic sites and/or unavailability of coenzyme. Long-latency convulsions after MDTC (0.12–0.37 mmol/kg) are comparable to those seen after TSC (0.27–2.2 mmol/kg) and may depend on a mechanism additional to inhibition of GAD.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 21 (1973), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: —The time course of effects of 2-deoxy-d-glucose on cerebral glucose metabolism has been studied in vivo and the inhibitory actions of 2-deoxy-d-glucose and 2-deoxy-d-glucose-6-phosphate on cerebral glycolytic enzymes in vitro. Mice were given 2-deoxy-d-glucose 3 g/kg intraperitoneally. Blood 2-deoxy-d-glucose/glucose ratio was 2–3 from 5 to 30 min after injection, the hyperglycaemic response to 2-deoxy-d-glucose having been suppressed with propranolol. Maximal cerebral 2-deoxy-d-glucose uptake observed was 1μ11 μmol/g/min between 5 and 10 min after injection. At 10 min brain concentrations of 2-deoxy-d-glucose and 2-deoxy-d-glucose-6-phosphate were 5·82 and 3·12 μmol/g. Analysis of the fate of d-[U-14C] glucose given subcutaneously 5 min before death showed that glucose uptake was reduced to 40–60 per cent of control from 5 to 30 min after 2-deoxy-d-glucose. However brain glucose concentration rose three to five-fold 20–30 min after 2-deoxy-d-glucose. The majority of glucose entering the brain after 10 min of 2-deoxy-d-glucose treatment was recovered as glucose. Conversion of brain glucose to other acid soluble components was reduced to 1/3 at 10 min and 1/5 at 20–30 min. Glucose-6-phosphate concentration rose from 5 min onwards and was maintained at twice control concentration from 10–30 min. However, because of the rapid entry of 2-deoxy-d-glucose and its conversion to 2-deoxy-d-glucose-6-phosphate, the 2-deoxy-d-glucose 6-P/glucose 6-P ratio was between 19 and 32. Brain adenosine triphosphate concentration did not change, creatine phosphate concentration fell after 25 min.Measurement of enzyme activities in cerebral homogenates (using 1 mivs substrate concentration) showed that hexokinase (EC 2.7.1.1) was 40 per cent inhibited by 5 mm-deoxy-d-glucose (but not by 2-deoxy-d-glucose 6-P). Glucose 6-P dehydrogenase (EC 1.1.1.49), 6-phosphogluconate dehydrogenase (EC 1.1.1.43) and phosphoglucomutase (EC 2.7.5.1) were not affected by either 2-deoxy-d-glucose (5 mm) or 2-deoxy-d-glucose 6-P (5 or 20 mm). Hexose-phosphate isomerase (EC 5.3.1.9) was 70 per cent inhibited by 20 mm-d-deoxy-d-glucose 6-P. Phosphofructokinase (EC 2.7.1.11) was inhibited by 17 per cent by 2-deoxy-d-glucose 6-P (20 mm). During the initial impairment of cerebral function by 2-deoxy-d-glucose there is competitive inhibition of glucose transport into the brain; later, glycolysis is more powerfully depressed by the inhibition of isomerase produced by the high intracerebral concentration of 2-deoxyglucose-6-phosphate.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 33 (1979), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— Regional changes in the concentration of GABA and pyridoxal phosphate were determined in rat brain after i.p. administration of convulsant doses of methyldithiocarbazinate (11 mg/kg), isonicotinic acid hydrazide (250 mg/kg) and thiosemicarbazide (25 mg/kg). At 15 and 30 min after methyldithiocarbazinate GABA concentrations were reduced in all brain regions (except ventral mid-brain). After 30 min the largest decrease was in the cerebellum (41%) and the smallest decrease in the hypothalamus (20%). Pyridoxal phosphate concentrations were decreased by 39-57%. After isonicotinic acid hydrazide. the regional decreases in GABA concentration were smaller and of slower onset than those seen after methyldithiocarbazinate. The pons-medulla was the first region to show a decrease (at 15 min) whereas a decrease was not seen in the frontal cortex until 45 min. Regional decreases in pyridoxal phosphate were smaller than those seen after methyldithiocarbazinate. After thiosemicarbazide, small regional decreases in GABA concentration were observed only in the hypothalamus, cerebellum, pons-medulla and posterior cortex (13-18%) and there was no apparent correlation between regional decreases in pyridoxal phosphate and regional decreases in GABA.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 30 (1978), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— The convulsant action of allylglycine (2-amino-4-pentenoic acid) is due to the metabolic conversion of allylglycine to 2-keto-4-pentenoic acid, a more potent glutamic acid decarboxylase inhibitor and more potent convulsant than the parent compound. We report regional changes in cerebral GABA concentration in rats after administration of d- and l-allylglycine. d-Allylglycine (3.75 mmol/kg) induced convulsions in 95–115 min, characterised by repeated clonic limb movements and rapid rotation around the head to tail axis. GABA concentrations were only reduced in cerebellum and ponsmedulla during the pre and post-convulsive periods. The localised reduction of GABA concentration is consistent with the enzymic conversion of d-allylglycine to 2-keto-4-pentenoic acid catalysed by cerebral d-amino acid oxidase, an enzyme known to be localised to the hind brain and spinal cord. l-allylglycine (1.2mmol/kg i.p.) induced convulsions in 65 -90 min, characterised by violent running followed by tonic flexion and extension. During the pre-convulsive period, GABA concentrations were reduced in all brain areas studied except the globus pallidus and ventral midbrain. The widespread decreases in GABA concentration suggest that the enzyme(s) which catalyse the conversion of l-allylglycine to 2-keto-4-pentenoic acid are widely distributed within the brain.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 26 (1976), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: —Brain glucose and glycogen concentrations have been studied in mice treated with allylglycine, 4-deoxypyridoxine and isoniazid, and the effects compared with the preconvulsive increase in brain glucose and glycogen concentration that follows d, l-methionine sulphoximine treatment. Allylglycine (180 mg/kg), 4-deoxypyridoxine (250 mg/kg), isoniazid (150 mg/kg) and d,l-methionine sulphoximine (300 mg/kg) when given to mice at room temperature, cause a fall in rectal temperature which can be prevented by maintaining the mice in an incubator at 33-34°C. An increase in brain glucose concentration is seen after allylglycine (+ 133%), d,l-methionine sulphoximine (+ 113%) and 4-deoxypyridoxine (+ 70%) treatment when mice are kept at room temperature and killed before convulsions occur. This is associated with a rise in blood glucose concentration after allylglycine, but not after the other drugs. Preventing the fall in rectal temperature reduces, but does not abolish, the rise in brain glucose concentration seen after allylglycine, d,l-methionine sulphoximine and 4-deoxypyridoxine. Brain glycogen concentration increases at room temperature after D,L-methionine sulphoximine and 4-deoxypyridoxine, but in mice with maintained body temperature only 4-deoxypyridoxine produces an increase in brain glycogen. Isoniazid does not increase brain glucose or glycogen at room temperature, but reduces their concentration in mice kept in the incubator. All four drugs are known to act on amino acid metabolism; d,l-methionine sulphoximine potently inhibits glutamine synthetase whereas 4-deoxypyridoxine, allylglycine and isoniazid inhibit glutamate decarboxylase. The connection, if any, between a block in the further metabolism of glutamate and an increase in brain glucose and glycogen is unknown.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 78 (1989), S. 53-59 
    ISSN: 1435-1463
    Keywords: [3H]5-HT binding ; human cortex ; calcium chloride ; ascorbic acid ; clorgyline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of different membrane preparations and assay conditions on [3H]5-HT binding to post-mortem human cortical tissue was studied. Optimal binding necessitated thorough removal of endogenous 5-HT and this was achieved either by hypotonic lysis or by preincubation of the membranes at 37
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1435-1463
    Keywords: Neuroleptics ; striatum ; substantia nigra ; GAD ; 3H-flunitrazepam binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats were treated continuously for 12 months with therapeutically equivalent doses of haloperidol (1.4–1.6 mg/kg/day), sulpiride (102–109 mg/kg/day) or clozapine (24–27 mg/kg/day) and examined for alterations in brain glutamic acid decarboxylase (GAD) and3H-flunitrazepam binding. Administration of haloperidol, but not sulpiride or clozapine, for 6 or 12 months increased striatal GAD activity. None of the drug treatments altered nigral GAD activity when examined after 1, 3, 6, 9 or 12 months administration. The number of specific3H-flunitrazepam binding sites (Bmax) in striatal membrane preparations were not altered by 12 months administration of haloperidol, sulpiride or clozapine. Surprisingly, Bmax for3H-flunitrazepam binding to cerebellar membrane preparations was decreased-by 12 months administration of all drug treatments. The dissociation constant (Kd) for3H-flunitrazepam binding in striatal and cerebellar preparations was not altered. The ability of GABA (0.25–100 μM) alone, and in conjunction with sodium chloride (200 mM), to stimulate specific3H-flunitrazepam binding in striatal and cerebellar preparations was unaltered by haloperidol, sulpiride or clozapine administration for 12 months. The selective effect of haloperidol, but not sulpiride or clozapine, treatment on striatal GAD activity parallels the ability of haloperidol, but not sulpiride or clozapine, to induce striatal dopamine receptor supersensitivity in the same animals. The actions of haloperidol may reflect its greater ability to induce tardive dyskinesia compared to sulpiride or clozapine.
    Type of Medium: Electronic Resource
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