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Biomedical subjects

T Serikawa

Publications and source records attributed to T Serikawa.

At least 73 records · Page 4Linked to original sources
PubMed1996

Cloning of the rat steroid sulfatase gene (Sts), a non-pseudoautosomal X-linked gene that undergoes X inactivation.

Although the human steroid sulfatase (STS) gene has been cloned and characterized in detail, several attempts to clone its mouse homologue, with either anti-human STS antibodies or human STS cDNA probes, have failed, suggesting a substantial divergence between these genes. However, partial amino-terminal sequence from purified rat liver STS is very similar to its human counterpart, and sequence comparisons have revealed several domains that are conserved among all the sulfatases characterized to date. Thus, we used a degenerate-primer RT-PCR approach to amplify a 321-bp fragment from rat liver cDNA, which was used as a probe to clone and characterize the complete cDNA. Comparison of the protein coding region between the rat and human genes showed 66% homology both at the DNA and the protein levels. STS activity was conferred to STS(-) A9 cells upon transfection with a rat Sts expression construct, indicating the authenticity of the cloned cDNA. While Sts has been shown to be located in the mouse pseudoautosomal region, both physical and genetic mapping demonstrate that Sts is not pseudoautosomal in the rat. The overall genomic organization of rat Sts and human STS is very similar, except that the insertion site for intron 1 in the rat is 26 bp upstream from that in the human. Rat Sts is only 8.2 kb long, while the human STS spans over 146 kb.

Amino Acid Sequence↗
PubMed1996

A rat mutation producing demyelination (dmy) maps to chromosome 17.

A recessive mutation exhibiting severe myelin breakdown, mainly at the level of the lumbar segments of the spinal cord and without any associated inflammation, was discovered in a partially inbred rat colony. Analysis of the segregation patterns of a set of polymorphic microsatellite markers in two inter-strain crosses allowed the mapping of this autosomal recessive mutation to rat Chromosome (Chr) 17, very close to the prolactin (Prl) locus, in a region homologous to human Chr 6p21.2-22.3 and mouse Chr 13. The pathology of the demyelination process and the chromosomal localization indicate that this mutation has no known equivalent in either mouse or human.

Animals↗
PubMed1996

Topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of spontaneously epileptic rats (SER).

The spontaneously epileptic rat (SER), a double mutant, manifests both tonic and absence-like seizures. The effect of topiramate, a novel antiepileptic drug, on the extracellular levels of excitatory amino acids (EAA) in the hippocampus of SER was investigated using in vivo microdialysis. The basal levels of glutamate and aspartate in dialysates of hippocampus in SER were 2- to 3-fold higher than those in normal Wistar rats. Both the dose-response relationship and the time course of the suppression of tonic seizures by topiramate were similar to the attenuation of glutamate level in SER. Topiramate (40 mg/kg i.p.) significantly (P < 0.05) reduced both glutamate and aspartate levels in SER while showing no effect on normal Wistar rats. These findings suggest that topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of SER. This effect may, at least in part, be related to the anticonvulsant activity of topiramate.

Animals↗
PubMed1996

Long-term antiepileptic effects of chronic intake of CNK-602A, a thyrotropin-releasing hormone analogue, on spontaneously epileptic rats.

Spontaneously epileptic rats (SER), which represent a double mutation (zi/zi, tm/tm), spontaneously exhibit both tonic and absence-like seizures. We examine the long-term effects of a thyrotropin-releasing hormone (TRH) analogue, CNK-602A, acute administration of which was effective inhibiting both types of seizures in SER, to determine if this agent could be used to treat epilepsy for long periods. Food pellets containing 0.001% CNK-602A were given ad libitum to SER from age 7 weeks. CNK-602A significantly inhibited tonic convulsions and prolonged survival. There were no alterations in body weight or plasma levels of triiodotHyronine (T3) and thyroxine (T4). These findings indicate that chronic intake of CNK-602A in a dose that does not affect plasma levels of T3 and T4 inhibits tonic convulsions in SER and suggest that this drug may be an effective treatment for convulsive seizures in patients with epilepsy.

Administration, Oral↗
PubMed1996

Analysis and comparison of new candidate loci for hypertension between genetic hypertensive rat strains.

To search for the genes that determine the level of blood pressure, we performed linkage analyses using rat microsatellite markers in two sets of F2 rats derived from two hypertensive rat strains and one normotensive rat strain. In the first F2 progeny obtained from spontaneously hypertensive rats and Wistar-Kyoto rats, it was found that two different loci cosegregated with blood pressure. One was gamma-crystallin locus on rat chromosome 9, which has a hypertensive effect, and the other was peroxisomal 3-keto acyl-CoA thiolase locus on rat chromosome 8, which has a hypotensive effect. Then, we studied the same loci in second F2 progeny obtained from Dahl/Iwai salt-sensitive rats and Wistar-Kyoto rats. It was found that the locus located on rat chromosome 8 also had a hypotensive effect, although the others were not cosegregated with blood pressure in this cross. We suggest that a new locus for hypertension is located on rat chromosome 9 and that a locus on rat chromosome 8 has a common effect that makes blood pressure decrease in different hypertensive strains.

Animals↗
PubMed1996

Genetic profiles of three inbred strains derived from wild rats (Rattus norvegicus) trapped in Japan.

In order to establish the genetic profiles of three inbred strains of rats (MITB/Yag, MITC/Yag and MITE/Yag; commonly designated as Mitake strains), which were derived from wild specimens of the Rattus norvegicus trapped in Mitake-cho, Gifu, Japan, 63 microsatellite markers were typed in these strains as well as nine other laboratory inbred strains. The data indicate that the MITB and MITC strains are very closely related (3% polymorphism between these strains), whereas the third strain MITE/Yag is relatively different from the other two strains (36% with the MITB, 39% with the MITC). Eighty-three to 58% of polymorphic loci had different alleles between the Mitake strains and the other strains, but 65-35% between the latter strains. In addition, 14 new alleles were found in the Mitake strains. These results suggest that the Mitake strains are useful for linkage analysis.

Animals↗
PubMed1996

Development of a novel rat mutant with spontaneous limbic-like seizures.

A new epileptic rat mutant with spontaneous seizures was developed by successive mating and selection from an inherited cataract rat. The procedures for developing the mutant and the symptomatology, electroencephalographic correlates, and neuropathology of the mutant are reported. It is possible that this rat stain will provide a useful animal model for human temporal lobe epilepsy. The seizures of the rat usually begin with face and head myoclonus, followed by rearing, and generalized clonic and tonic convulsions, all of which are symptomatologically the same as limbic seizures. Electrographic recording during generalized convulsive seizures demonstrated that sustained spike discharges emerged at the hippocampus and then propagated to the neocortex. Seizures occurred spontaneously without any artificial stimuli. Furthermore, external stimuli such as auditory, flashing light, or vestibular stimulations could not elicit epileptic attacks. Almost all of the male animals had generalized convulsions, mostly from 5 months after birth, and the frequency of the seizures increased with aging. Generalized convulsions developed in approximately 20% of the female rats. Microdysgenesis, such as abnormal neuronal clustering, neuronal disarrangement, or interruption of pyramidal neurons in the hippocampal formation, was found in the young rats that had not yet had generalized seizures. This microdysgenesis, which is though to be genetically programmed, was very interesting from the aspect of the relationship between structural abnormalities and epileptogenesis in this mutant. In addition to microdysgenesis, there was sprouting of mossy fibers into the inner molecular layer of the dentate gyrus in those adult rats that had repeated generalized convulsions. An increase of glial-fibrillary-acidic-protein-positive astrocytes with thickened and numerous processes, ie, astrogliosis, was also found in the cerebral cortex, amygdala region, and hippocampus of these adult animals. Judging from the characteristics of the symptomatology, electroencephalographic correlates, and neuropathology, this epileptic mutant can be expected to be a useful animal model for studying human temporal lobe epilepsy.

Aging↗
PubMed1995

Effect of nicardipine on abnormal excitability of CA3 pyramidal cells in hippocampal slices of spontaneously epileptic rats.

The effects of nicardipine, a Ca2+ channel antagonist, on the abnormal excitability of hippocampal CA3 neurons in spontaneously epileptic rats (SER), a double mutant (zi/zi, tm/tm), were examined to elucidate whether or not the abnormality was due to that of Ca2+ channels. An intracellular recording study was performed using brain slice preparations of SER 12-15 weeks of age, when SER showed both tonic convulsions and absence-like seizures. Bath application of nicardipine (10 nM) completely inhibited the depolarizing shifts lasting for 60-120 ms and accompanying repetitive firings on mossy fiber stimulation in SER. However, this drug did not affect the single action potential induced by the mossy fiber stimulation in CA3 neurons of SER and normal Wistar rats. In the CA3 pyramidal neurons of SER, the Ca2+ spikes induced by the depolarizing pulse applied in the cell in the presence of tetrodotoxin and tetraethylammonium had a different configuration from that in normal Wistar rats. Nicardipine also inhibited the Ca2+ spikes in SER CA3 neurons at a concentration (1 nM) that had no effect on those in normal Wistar rats, while the Ca2+ spikes in Wistar rat CA3 neurons were inhibited by 10 nM nicardipine. These findings suggest that the abnormal excitability of CA3 pyramidal neurons in SER might be attributed to abnormalities of the Ca2+ channels, and that the Ca2+ channel antagonist may be effective as an antiepileptic drug.

Animals↗
PubMed1995

The SMXA: a new set of recombinant inbred strain of mice consisting of 26 substrains and their genetic profile.

A new set of recombinant inbred (RI) strain SMXA consisting of 26 substrains was established between SM/J and A/J. The history of the SMXA RI strains and their genetic profile covering 158 genetic marker loci are reported. From the strain distribution pattern among SMXA RI strains, the chromosomal location of salivary and tear protein genes Spe1-r, Spe1-s, Spe2, and Tpe1 were newly determined.

Animals↗
PubMed1995

Altered brain contents of neuropeptides in spontaneously epileptic rats (SER) and tremor rats with absence seizures.

Immunoreactive- (IR-) somatostatin (SRIF), neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) contents were investigated in the brain of tremor rats with absence-like seizure and spontaneously epileptic rats (SER), which is a genetically defined double-mutant (zi/zi, tm/tm) obtained by mating zitter homozygote (zi/zi) with tremor heterozygote (tm/+) and shows both absence-like seizure and tonic convulsions. Increased levels of IR-NPY and IR-CRF were observed in several regions including the amygdala and hippocampus in homozygous SER compared to heterozygous SER (zi/zi, tm/+ or +/+). Homozygous tremor rats (tm/tm) showed lower levels of IR-NPY and IR-CRF contents mainly in the hippocampus and mesolimbic system (entorhinal and pyriform cortex and nucleus accumbens) than heterozygous tremor rats. IR-SRIF contents of homozygous SER were higher in frontal cortex than heterozygous SER and in amygdala than homozygous tremor rats. No change of IR-SRIF between groups was noted in the hippocampus among brain structures underlying epileptogenicity. The results suggest that the change of neuropeptide levels, most conspicuous in NPY among three peptides tested, may be involved in the phenotypical manifestation of seizures in SER and tremor rats, and that the development of tonic convulsion and absence seizures may be differently associated with the change of brain neuropeptide levels.

Animals↗
PubMed1995

[125I]iomazenil binding in the brains of spontaneously epileptic rats: an ex vivo quantitative autoradiographic study.

Central benzodiazepine receptor binding was studied in spontaneously epileptic rats (SER) and in their parent strain. Kyoto-Wistar (KW) rats, by ex vivo quantitative autoradiography with [125I]iomazenil. Thirteen-week-old SER developed tonic and absence-like seizures following mild stimulation by tapping at 5 min before injection of the radioligand. When compared with age-matched KW rats, a significant 76% elevation of radioactivity was observed in the SER hippocampus, while there was no difference in hippocampal blood flow obtained using [125I]N-isopropyl-p-iodoamphetamine. Since benzodiazepine receptors act to enhance inhibitory GABA transmission, this finding suggests a possible mechanism for seizure-induced enhancement of inhibition.

Animals↗
PubMed1995

Effect of antiepileptic drugs on absence-like seizures in the tremor rat.

We examined the effects of conventional antiepileptic drugs (AEDs) on absence-like seizures in homozygous tremor rats (tm/tm) to determine if they corresponded pharmacologically to human absence seizures and absence-like seizures in spontaneously epileptic rats (SER: zi/zi, tm/tm) with both tonic convulsive and absence-like seizures. Cortical and hippocampal EEG activity was recorded with chronically implanted electrodes. The effects of AEDS on seizures of the tremor rat showed profiles similar to those observed in human absence seizures and also in absence-like seizures of SER. The absence-like seizures, associated with paroxysmal bursts of 5-7-Hz spike-wave complexes, were inhibited by trimethadione (TMO 200 mg/kg intraperitoneally, i.p.), ethosuximide (ESM 100 and 200 mg/kg, i.p.), valproate (VPA 100 mg/kg, i.p.), and phenobarbital (PB 10 and 20 mg/kg, i.p.). Phenytoin (PHT 20 mg/kg, i.p.) was ineffective. These results are consistent with the conclusion that the tremor rat is a useful model for evaluating new AEDS for human absence seizures.

Animals↗
PubMed1995

Gap junction protein locus on chromosome 18 cosegregates with body weight in the spontaneously hypertensive rat.

To detect genetic predisposing factors for hypertension, we screened the genome of the spontaneously hypertensive rat (SHR). We determined the genotypes of all F2 rats at polymorphic sites between the two strains, using the DNA of F2 rats derived from mating of SHR and Wistar-Kyoto rats (WKY). Cosegregation analysis was conducted to assess whether the genotypes of polymorphic markers associate with any phenotypic parameters such as directly measured blood pressure, heart rate or body weight. All measurements in F2 rats were performed at 15 weeks of age. Two polymorphic markers on chromosome 18 cosegregated with body weight. Gap junction protein (heart connexin 43) gene showed the most significant association with body weight as a recessive trait, but no association was noted with other parameters. We conclude that the gap junction protein locus is a new candidate for the determinant gene of body weight in SHR.

Analysis of Variance↗
PubMed1995

Fourteen anonymous DNA markers of laboratory rats identified with arbitrarily primed polymerase chain reaction (AP-PCR).

In order to develop genetic markers in rats, arbitrarily primed polymerase chain reaction (AP-PCR) was performed with single primers originally designed for microsatellite loci, instead of primers with short-sized and arbitrary nucleotide sequences. Each primer generated reliable and reproducible segments under optimal conditions. The fourteen amplification products have been successfully mapped to rat chromosomes by either linkage analysis using backcross progeny or chromosomal assignment with somatic cell hybrids. All of the loci were located on different chromosomes from those of the microsatellite loci, suggesting that sequence-specifically designed single primers can produce anonymous segments of genomic DNA showing polymorphisms. These markers should contribute to finding linkages for traits of interest in rats.

Animals↗