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Y L Murashima

Publications and source records attributed to Y L Murashima.

At least 19 recordsLinked to original sources
PubMed2000

Cellular mechanism of action of cognitive enhancers: effects of nefiracetam on neuronal Ca2+ channels.

Cellular mechanisms underlying the cognition-enhancing actions of piracetam-like nootropics were studied by recording Ca2+ channel currents from neuroblastoma x glioma hybrid (NG108-15) cells and Xenopus oocytes expressing Ca2+ channels. In NG108-15 cells, nefiracetam (1 microM) produced a twofold increase in L-type Ca2+ channel currents. A similar, but slightly less potent effect was observed with aniracetam, whereas piracetam and oxiracetam exerted no such effects. Cyclic AMP analogs mimicked the nefiracetam action. N-type Ca2+ channel currents inhibited by leucine (Leu)-enkephalin by means of inhibitory G proteins (Go/Gi) were recovered promptly by nefiracetam, whereas those inhibited by prostaglandin E1 via stimulatory G proteins were not affected by nefiracetam. Cells treated with pertussis toxin (500 ng/mL, > 20 hours) were insensitive to nefiracetam. In Xenopus oocytes functionally expressing N-type (alpha1B) Ca2+ channels and delta-opioid receptors, nefiracetam was also effective in facilitating the recovery from Leu-enkephalin-induced inhibition. These results suggest that nefiracetam, and possibly aniracetam, may activate N- and L-type Ca2+ channels in a differential way depending on how they recover from Go/Gi-mediated inhibition.

Animals↗
PubMed2000

Role of nitric oxide in the epileptogenesis of EL mice.

PURPOSE: To understand the role of nitric oxide (NO) in the regulation of seizures, we measured the extracellular levels of the NO metabolites nitrite and nitrate as indices of NO generation in the parietal cortex, hippocampus, and temporal cortex of EL mice. Furthermore, alterations of neuronal, endothelial, and inducible nitric oxide synthetase (nNOS, eNOS, and iNOS, respectively) were observed to correlate them with epileptogenesis. METHODS: EL mice of 20 weeks and 30 weeks of age (before and after the establishment of epileptogenesis, respectively) were used. Nitrite was quantified using the specific absorbancy of diazo dye. NOS isoenzymes (nNOS, iNOS, and eNOS) were also investigated in the hippocampus during development until mice were 30 weeks old. Samples (total protein, 8.33 to 8.43 microg) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and identified by immunoblotting. RESULTS: EL mice that experienced repetitive seizures showed a remarkable increase in nitrite in the hippocampus at 30 weeks of age compared with EL mice that had no experience of seizures. nNOS and iNOS were major and minor components, respectively, and both increased in parallel with the development of epileptogenesis. eNOS was not detectable. CONCLUSIONS: Excess iNOS (and subsequent increase in harmful NO) and deficient eNOS (and subsequent decrease in NO identified as an endothelium-derived relaxing factor) may work together to form a focus complex.

Animals↗
PubMed1999

Two types of aggregate in the cerebral cortex of a seizure-sensitive strain of the Mongolian gerbil.

A 70-kDa protein, P70, found mostly in the pyramidal cells of the cerebral cortex of cobalt-induced epileptogenic rats, has been implicated in epileptogenesis. The presence of a P70-like substance was searched for immunohistochemically in the cerebral cortex of MGS/ldr, a seizure-sensitive strain of the Mongolian gerbil (Meriones unguiculatus) that we previously established. Immunoreactive aggregates were observed in the pyramidal neurons of the motor cortex and the primary somatosensory cortex. Analysis using confocal laser scanning microscopy revealed that the aggregates were often colocalized with a second type of aggregate with red autofluorescence at the marginal zone of the cell somata. Both aggregates appeared and increased before the appearance of generalized tonic-clonic convulsion. These may be involved in some change of physiological function of the cerebral cortex but their presence itself is not enough to determine the occurrence of epileptic seizure because the gerbils that showed no such seizure had both aggregates.

Animals↗
PubMed1998

Antiepileptic effects of allopurinol on EL mice are associated with changes in SOD isoenzyme activities.

We have investigated the potential antiepileptic action of superoxide dismutase (SOD) activities in the brain of the epileptic mutant EL mouse. EL mice which experienced frequent seizures (EL[s]) had abnormally low levels of SOD isoenzyme activity in the hippocampal area. Once epileptogenicity was established in these animals, activity of cyanide-sensitive Cu,Zn-SOD was maintained at significantly lower levels than in control mice. However, cyanide-insensitive Mn-SOD activity was not different from non-epileptic controls. In EL mice which had not experienced seizure provoking stimulations and exhibited no seizures (EL[ns]) there was moderately lower levels of SOD isoenzyme activities compared to controls. In spite of the low level of Cu,Zn-SOD activity in EL[s] mice, the Cu,Zn-SOD protein content was high in the hippocampus of these animals, suggesting that inactive Cu,Zn-SOD might be induced during development. After allopurinol (ALP) was given orally to EL[s] mice, Cu,Zn-SOD activities increased dramatically in the hippocampus and seizure activity was decreased. Even after 48 h, when antiepileptic action of ALP was lost, the SOD activity was maintained at the high level associated with initial ALP administration. EL[s] mice also showed DNA fragmentation in the hippocampal CA1 region and the parietal cortex, detected with in situ terminal transferase-mediated dUTP nick labeling with the aid of alkaliphosphatase or peroxidase. The degree of DNA fragmentation was less severe in EL[ns] mice. We propose that abnormalities in region specific Cu,Zn-SOD isoenzyme activity might produce free radicals, leading to DNA fragmentations and cell loss. This might contribute to hippocampal epileptogenesis in EL mice.

Allopurinol↗
PubMed1996

Developmental and seizure-related regional differences in immediate early gene expression and GABAergic abnormalities in the brain of EL mice.

To examine the hypothesized role of the immediate early gene (IEG) response in synaptic plasticity and in epileptogenesis, we studied the spatial specificity of the expression of IEG in EL mice, a well known mutant model of epilepsy. Also to examine the 'GABA hypothesis' in epilepsy, GABA concentration and GAD activity was determined in micro brain regions (10-300 ng) of EL mice related to the focus in the parietal cortex and the hippocampus. We found that the IEG expression after seizures is not related to the seizure pattern, but to the seizure history, seizure threshold and development of EL[s]. Even in the interictal period, EL mice with long seizure histories and very low seizure thresholds demonstrate IEG expression continuously. This is probably strengthened by repeated seizures. The IEG expression site is however located in the hippocampal CA1, which is the final terminal of various inputs from other areas of the limbic system. It is proposed that the continuous expression of IEGs might play a different role from that of transiently expressed IEGs. Developmentally, the site of IEG expression shifted from one site to another in a very similar manner as in the IEG expression with propagation of paroxysmal discharges in each seizure, and the three-dimensional expression area was gradually expanded, suggesting a change in the regional active site during epileptogenesis. These lines of evidence suggest that during development as well as repetitive seizures, frequent expressions of IEGs and syntheses of Fos and Zif proteins might facilitate synaptic conductivity involved in epileptogenesis. The sites of abnormal GABA concentrations and GAD activities were almost the same in the parietal cortex, around Sidman atlas coronal section No. 300 and in the hippocampal CA1 pyramidal cells as the spatio-temporal specific IEG expression sites. These findings strongly suggest that IEG expression and abnormal GABAergic functions are involved in epileptogenesis in EL mice.

Animals↗
PubMed1994

Alcohol consumption and insomnia in a sample of Japanese alcoholics.

The amount of ethanol consumed by chronic alcoholics in a Japanese slum area with persistent insomnia (n = 40) and those without it (n = 40) was compared using a questionnaire. For both groups, the present habitual consumption (PHC) of ethanol per day was most frequently between 60 g and 150 g and no difference was observed between the two groups. In contrast, the maximum habitual consumption (MHC) of ethanol per day throughout the alcoholic history was found to be greater for the insomnia patients than the non-insomniacs (p < 0.001). No difference between the groups was found in the kind of alcoholic drink consumed, with sake (Japanese rice wine) being the most popular in both groups. The results suggest that persistent insomnia in alcoholics is related to excessive alcohol intake and persists even when drinking levels have fallen.

Adult↗
PubMed1990

gamma-Aminobutyric acid system in developing and degenerating mouse retina.

Freeze-dried sections (14 microns thick) of retinal layers were prepared from mice with retinal degeneration (C3H strain) and control mice (C57BL strain). The weighed sections (2-30 ng dry weight) were analyzed using our microassay methods. In the control retina, gamma-aminobutyric acid (GABA) concentration and glutamate decarboxylase (GAD) activity, on a dry weight basis, increased from birth to 9 weeks of age and decreased slightly at 20 weeks. In the degenerated retina, the levels of GABA and GAD activity were higher at birth than in the control retina, and continued to increase until 20 weeks of age, at which time the GAD activity reached a markedly high level. This increase was found when the total GABA and GAD levels per retina were determined. In the normal retinal layers, GABA and GAD were confined primarily to the inner plexiform layer. In the degenerated retina, GAD activity gradually increased in the inner layers during postnatal development, but by 20 weeks the increase was most prominent in the inner part of inner nuclear layer and in the outer part of inner plexiform layer. GABA transaminase activity and its distribution were not much different in both normal and degenerated retinas during development.

Animals↗