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T Shohmori

Publications and source records attributed to T Shohmori.

At least 37 records · Page 2Linked to original sources

Neurotransmitter interactions in the striatum and hypothalamus of mice after single and repeated ethanol treatment.

In single treatment study, ethanol was administered intraperitoneally to ICR mice (about 34 g) in the amounts of 1.0, 2.0, 3.0 or 4.0 g/kg body weight. The 3,4-dihydroxyphenylacetic acid (DOPAC) + homovanillic acid (HVA) concentration in the striatum was elevated with 3.0 and 4.0 g/kg of ethanol. In the hypothalamus, the DOPAC, HVA and 5-hydroxyindoleacetic acid concentrations were increased after injection of 3.0 and 4.0 g/kg of ethanol. Furthermore, the acetylcholine (ACh) and gamma-aminobutyric acid (GABA) concentrations were also increased following the injection of 1.0, 2.0, 3.0 and 4.0 g/kg. To study the effects of repeated administration, mice were injected intraperitoneally with 1.0 or 2.0 g/kg of ethanol once daily for 7 days. The DOPAC + HVA level in the striatum was elevated after injection of 1.0 and 2.0 g/kg of ethanol. The GABA and ACh concentrations in the hypothalamus were decreased after repeated injections of ethanol. These results suggest that ethanol significantly alters the utilization of dopamine, ACh and GABA in the hypothalamus. This may partially explain why ethanol has such profound effects on emotional behavior and mood.

Animals↗

Detection of endogenous albumin as an index of blood parenchymal border alteration.

We used a microdialysis technique to establish a method to detect sequential changes in disruption of the blood parenchymal border. Twelve cats were divided into two groups; one group underwent occlusion of the middle cerebral artery for 60 minutes, the other a cold injury model. Microdialysis probes were implanted bilaterally into the white matter, and dialysates were collected successively at 30 minute intervals for 6 hours in the occlusion model and 4 hours in the cold injury model. Regional cerebral blood flow was measured simultaneously using the hydrogen clearance method. The water content of the white matter was measured using specific gravity. The proteins in the dialysate were analyzed using electrophoresis with silver stain, and, with densitometric analysis, the density of the 66.2 kDa band was quantified as albumin. The ratio of this density to the preoperative density was defined as the "albumin index." On the side of the lesion in the cold injury model, this index significantly increased 3 hours after the cold injury compared with the contralateral side, and a correlation between the water content and this index was observed. The albumin index was believed to indicate the severity of disruption of the blood parenchymal border.

Animals↗

Changes in muscarinic cholinergic, PCP, GABAA, D1, and 5-HT2A receptor binding, but not in benzodiazepine receptor binding in the brains of aged rats.

We used in vitro quantitative autoradiography to investigate changes in neurotransmitter receptor binding, including muscarinic cholinergic, PCP, GABAA, benzodiazepine, D1 and 5-HT2A receptor, in the brains of aged rats, compared with such binding in young rats. Scatchard analysis revealed that the maximal number of binding sites for [3H]quinuclidinyl benzilate (QNB) in the caudate/putamen and accumbens was significantly decreased in aged rats compared with young rats, while its affinity remained unchanged. The specific binding of [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine (TCP) for the ion channels coupled with N-methyl-D-aspartate receptors in the caudate/putamen and hippocampus was significantly decreased in aged rats compared with young rats. The [3H]muscimol binding in aged rats was decreased in all brain regions examined compared with that in young rats, whereas [3H]flunitrazepam binding was not changed in any brain regions. The [3H]SCH23390 binding for dopamine D1 receptors was significantly increased in the parietal cortex, but decreased in the caudate/putamen and accumbens of aged rats compared with that in young rats. The [3H]ketanserin binding for 5-HT2A receptors in the cortex and accumbens was significantly decreased in aged rats compared with young rats. These results suggest that uneven changes in receptors for various neurotransmitters throughout the brain may be responsible for the decline of brain function in aged rats.

Aging↗

Effects of kamikihito, a traditional Chinese medicine, on neurotransmitter receptor binding in the aged rat brain determined by in vitro autoradiography: changes in dopamine D1 and serotonin 5-HT2A receptor binding.

Using in vitro autoradiography, we investigated the effects of Kamikihito (KKT), a traditional Chinese medicine, on specific [3H]SCH23390 binding to dopamine D1 receptors and [3H]ketanserine binding to serotonin 5-HT2A receptors in the rat brain. Specific binding of both compounds was affected by aging. Long-term administration of KKT resulted in decreases in [3H]SCH23390 binding to the cortex and hippocampus in aged rats, and in decreases in [3H]ketanserine binding to the caudate/putamen in young rats. These results suggest that the changes in dopamine Di and serotonin 5-HT2A receptor binding may be involved in the central effects of KKT.

Aging↗

Effects of kamikihito, a traditional Chinese medicine, on neurotransmitter receptor binding in the aged rat brain determined by in vitro autoradiography (1): Changes in the [3H]QNB binding.

Using in vitro autoradiography, we investigated the effects of Kamikihito (KKT), a traditional Chinese medicine, on the specific binding of [3H]quinuclidinyl benzilate (QNB) and [3H]N-(1-[2-thienyl]cyclohexyl)-3,4-piperidine (TCP) in the rat brain. The Bmax but not the Kd values for [3H]QNB binding to the caudate/putamen and accumbens in aged rats were lower than those in young rats. The [3H]TCP binding was also decreased in aged rats compared with that in young rats. Long-term administration of KKT modulated the [3H]QNB binding in young but not aged rats.

Aging↗

Effects of Kamikihito, a traditional Chinese medicine, on neurotransmitter receptor binding in the aged rat brain determined by in vitro autoradiography (2): changes in GABAA and benzodiazepine receptor binding.

We investigated the effects of the long-term administration of Kamikihito (KKT) on the specific binding of [3H]muscimol and [3H]flunitrazepam in the brains of young and aged rats using in vitro quantitative autoradiography. Specific [3H]muscimol binding in aged rats was decreased in all brain regions examined compared with that in young rats, whereas [3H]flunitrazepam binding did not change in any of the brain regions. Scatchard analysis revealed that the maximal number of [3H]muscimol binding sites in the cortex and thalamus was significantly decreased in aged rats compared with young rats, while its affinity remained unchanged. Long-term administration of KKT in young rats had no effect on either [3H]muscimol or [3H]flunitrazepam binding. In contrast, the same treatment in aged rats produced a significant increase in [3H]flunitrazepam binding to the cortex, caudate/putamen and accumbens, and it tended to decrease the [3H]muscimol binding. These results suggest that the selective reduction of specific [3H]muscimol binding in the brain may be responsible, at least in part, for anxiety-related behavior in aged rats. Furthermore, it appears that the significant increase in specific [3H]flunitrazepam binding produced in the brains of aged rats by the long-term administration of KKT may be responsible for the anxiolytic effects of this agent.

Aging↗

Molecular cloning of partial cDNAs for rat DNA topoisomerase II isoforms and their differential expression in brain development.

cDNA segments for DNA topoisomerase II were amplified from rat brain RNA after reverse transcription by the polymerase chain reaction, using degenerate oligonucleotide primers deduced from the conserved regions of topoisomerase II of higher eukaryotes. The cDNA product from a successful amplification was homogeneous in length but heterogeneous in sequence. Restriction mapping of the cloned cDNA fragments revealed that they consisted of two distinct sequence groups. DNA sequencing of representative clones from each group, designated A and B, showed that they are highly homologous to cDNAs of human topoisomerase II isoforms, alpha and beta, respectively. Northern blot analysis indicated that the transcript level for rat topoisomerase II alpha was high in embryonic brain and in the cerebellum of 2-day newborns, followed by rapid decrease to a undetectable level at 4 weeks after birth. In contrast, rat topoisomerase II beta transcript was present throughout the embryonic and postnatal stages. In the developing cerebellum, cells expressing topoisomerase II alpha were confirmed exclusively to the outer mitotic zone of the external granular layer, whereas the transcript of topoisomerase II beta was detected over the entire cortical region. These results clearly indicate that the isoform alpha is expressed only in proliferating cells. The differential expression of topoisomerase II isozymes was also observed among developed tissues. Therefore, the isozymes are most likely to be involved in the following different physiological processes: topoisomerase II alpha in cell proliferation, and topoisomerase II beta in some processes unrelated to cell proliferation.

Amino Acid Sequence↗

Identification and characterization of a nuclear scaffold protein that binds the matrix attachment region DNA.

The association of nuclear DNA with the nuclear matrix (scaffold) is mediated by defined segments of DNA called matrix association region (MAR). By using a plasmid harboring a portion of the Ig kappa gene within which MAR had been located, we searched for proteins recognizing MAR in the nuclear scaffold components electrophoretically separated and blotted onto a membrane. In the presence of nonspecific competitor DNA, the labeled plasmid selectively bound to a protein with apparent molecular weight of 120,000 (designated SP120). The protein was purified directly from SDS-polyacrylamide gels and renatured by a guanidine hydrochloride procedure. The DNA region in the plasmid responsible for the binding to the solubilized SP120 coincided with the 365-base pair HindIII-HinfI fragment that had been identified as MAR. In solution, SP120 exhibited a cooperative mode of interaction with the end-labeled MAR fragment. Measurement of relative affinities of MAR subfragments to SP120 showed that the whole region is required for efficient binding. This is consistent with the minimal length for MAR estimated thus far by in situ mapping experiments. The MAR derived from another gene, fushitarazu, also bound specifically to SP120. Immunostaining of whole cells and isolated nuclei with a monoclonal antibody raised against SP120 indicated that the protein is localized in a nuclear skeletal structure. These results suggest the involvement of SP120 in the MAR-mediated anchorage of nuclear DNA to the nuclear scaffold.

Animals↗

[High-field-strength magnetic resonance imaging and SPECT of multiple system atrophy].

Two cases of multiple system atrophy (MSA) showing similar abnormalities by magnetic resonance (MR) imaging and SPECT are reported. The clinical diagnoses of the two cases were striatonigral degeneration (SND) and sporadic olivopontocerebellar atrophy (OPCA). In addition, one case of sporadic OPCA without parkinsonism was used for comparison. The MR images were obtained using a 1.5-T MR system and included spin-echo transverse sections with T1-weighted images (TR = 450 ms and TE = 15 ms) and T2-weighted images (TR = 2500 ms and TE = 90 ms). The T1-weighted images demonstrated atrophy of cerebellum and pons, with increased signal intensity in the bilateral putamen. The T2-weighted images demonstrated decreased signal intensity in the putamen, as reported recently. SPECT demonstrated reduced uptake in the celleberum, basal ganglia and frontal lobe cortex. The putaminal changes evident on T1-weighted images may have resulted from deposition of pigments such as neuromelanin and lipofuscin, related to parkinsonism. Both T1- and T2-weighted MRI seem to be useful clinical diagnosis of MSA.

Brain↗

[Diffuse reduced uptake in 99m-Tc-HM-PAO SPECT and high level of neuron-specific enolase in cerebrospinal fluid in the early stage of Creutzfeldt-Jakob disease].

We report an autopsy-diagnosed case of Creutzfeldt-Jacob disease (CJD) showing diffuse reduced uptake in SPECT and a high level of neuron-specific enolase (NSE) in the cerebrospinal fluid (CSF). A 75-year-old woman with a 3-month history of progressive gait ataxia and dementia was examined. Four months after onset of the disease, she developed an akinetic mutism with normal CT and MRI. She was admitted for further examination, and electroencephalography showed periodic synchronous discharges. NSE in the CSF showed a high level at 90.6 ng/ml, and SPECT showed diffuse reduced uptake in the supratentorial region, with relatively spared uptake in the cerebellum. She died 13 months after onset of the disease, and the autopsy diagnosis was CJD. SPECT data and the level of NSE in CSF seem to be useful for clinical diagnosis and pathogenetic analysis in the early stage of CJD.

Aged↗

[A case of encephalitis with MRI abnormalities localized in the bilateral amygdala and hippocampus].

We report a patient with encephalitis who showed anterograde and retrograde amnesia with MRI abnormalities localized in the bilateral amygdala (AM) and hippocampus (HIPP). A 25-year-old man suddenly experienced a generalized tonic-clonic seizure (GTCS). He was admitted because of increasing lethargy with two further GTCSs during the following 6 days. The patient had high fever, and neurological examination revealed somnolence, disorientation, amnesia, and nuchal stiffness. MRI revealed bilateral symmetrical abnormalities localized in the AM and HIPP, which showed low intensity on T1-weighted images and high intensity on T2-weighted images. Cerebrospinal fluid examination showed a mildly elevated cell count. We suspected herpes simplex virus type I encephalitis and began treatment with acyclovir. After the patient regained a clear consciousness, his antero- and retrograde amnesia continued for several months. The MRI abnormality became less distinct with the improvement of amnesia. We consider that the MRI abnormality was indicative of inflammation and edema, and that the lesion in the AM and HIPP had induced the amnesia.

Acyclovir↗

The effect of acute and repeated ethanol administration on monoamines and their metabolites in brain regions of rats.

Concentrations of norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in eleven brain regions of rats following acute and repeated ethanol administration: (a) an intraperitoneal (i.p.) injection of 1, 2, 3 or 4g ethanol/kg body weight and (b) i.p. injection of 1 or 2g ethanol/kg body weight for seven consecutive days. After acute administration, the concentrations of monoamines and their metabolites appeared to be altered in all brain regions examined except substantia nigra and dorsal amygdala, with maximal variation 2 or 3h after 3g ethanol administration. After repeated administration, the alterations following injections of 2.0g/kg were more marked than the injections of 1.0g/kg. Generally, the levels of NE, DA and 5-HT were decreased while the levels of HVA, DOPAC and 5-HIAA were increased with a few exception. The most prominent findings were seen in the striatum, nucleus accumbens and locus coeruleus. These data indicate that concentrations of monoamines and their metabolites can be determined simultaneously in discrete brain regions and that monoaminergic systems in the brain respond region-specifically to ethanol treatment.

Alcoholism↗

Comparative study of sulpiride and haloperidol on dopamine turnover in the rat brain.

The effects of the neuroleptics, sulpiride and haloperidol, on dopamine (DA) turnover were compared following the acute and chronic administration of these drugs alone or in combination with levodopa or apomorphine. In the acute treatment, the increase in DA metabolites in the striatum and nucleus accumbens was more marked in the haloperidol-treated rats than in the sulpiride-treated rats. Following the additional administration of levodopa, however, the potency of the neuroleptics in elevating DA metabolites was reversed. A low dose of apomorphine induced a marked reduction in the striatal DA metabolite levels by approximately 50%. When rats were pretreated with the neuroleptics, haloperidol was more effective in preventing an apomorphine-induced reduction in DA metabolites. On repeated administration of the neuroleptics, a tolerance occurred in the striatum and nucleus accumbens, but not in the prefrontal cortex. This differential development of tolerance was observed in the different brain regions and with the different drugs administered. These results suggest that the pharmacological mechanism of sulpiride on DA turnover differs from that of haloperidol.

3,4-Dihydroxyphenylacetic Acid↗

Action of peripherally administered cholecystokinin on monoaminergic and GABAergic neurons in the rat brain.

In an acute study, cholecystokinin octapeptide sulfate (CCK) in doses of 1, 10 or 100 micrograms/kg body weight was injected intraperitoneally into rats just prior to the dark cycle. Rats were sacrificed two hours following the CCK injection. Norepinephrine levels were elevated in the dorsal amygdala of rats injected with 10 micrograms of CCK as well as in the septum of rats injected with 1 and 10 micrograms of CCK. The dopamine level in the septum of rats injected with 1 microgram of CCK as well as the gamma-aminobutyric acid (GABA) level in the lateral hypothalamus of rats injected with 10 micrograms of CCK were also elevated. In a chronic study, CCK (1 microgram/kg body weight/h) was subcutaneously infused into rats with Alzet osmotic minipump for seven consecutive days. The daily food consumption did not change during the 7 days of CCK infusion. The dopamine turnover in the striatum accelerated and the GABA level increased. On the contrary, dopamine metabolism in the substantia nigra and locus coeruleus decreased. Furthermore, the serotonin level in the substantia nigra decreased. Norepinephrine levels decreased in the nucleus paraventricularis, the locus coeruleus and the substantia nigra. The results suggest that peripherally administered CCK may act on the monoaminergic neurons and GABAergic neurons in the brain.

3,4-Dihydroxyphenylacetic Acid↗

Effect of long-term storage on monoamine metabolite levels in human cerebrospinal fluid.

Concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in human cerebrospinal fluid (CSF) following long-term storage at -20 degrees C for intervals of three to 60 months. No significant changes in HVA levels were detected in CSF stored for up to 60 months. On the other hand, 5-HIAA concentrations remained stable for up to 6 months, but decreased significantly in the specimens stored for longer time intervals. The results indicate that 5-HIAA should be determined within 6 months after CSF collection, while HVA determinations may be delayed.

Chromatography, High Pressure Liquid↗

Levels of topoisomerase II and DNA polymerase alpha are regulated independently in developing neuronal nuclei.

A possible correlation between activity levels of topoisomerase II and DNA polymerase alpha was studied in neuronal nuclei from developing rat brain. A high level of canonical topoisomerase II activity was detected in neuronal nuclei throughout the development even at a late stage (28 days after birth) when the activity of DNA polymerase alpha decreased to less than 2% of the fetal level. Thus, in contrast to other systems, topoisomerase II does not change in parallel with DNA polymerase alpha during neuronal development. Our results suggest that topoisomerase II is required to maintain some fundamental processes in differentiated cells, including transcription.

Age Factors↗

Determination of phenylacetic acid in cerebrospinal fluid by gas chromatography-mass spectrometry.

Using gas chromatography-mass spectrometry, we developed a sensitive and reliable technique to measure phenylacetic acid (PAA), an oxidatively deaminated metabolite of beta-phenylethylamine (PEA), in small amounts of cerebrospinal fluid (CSF). In a preliminary analysis, PAA concentrations in depressive patients were significantly lower than those in controls, while there were no differences in PAA levels between schizophrenic patients and controls. This suggests a possible link between the decreased PEA metabolism in the brain and the etiology of depression. However, further studies are needed to clarify the effects of neuroleptics and antidepressants on PAA levels in CSF, since the samples were obtained without regard to medication in the present study. In control subjects, a U-shaped distribution was obtained when the values of PAA were plotted as a function of age. There were no sex differences and no significant concentration gradients in CSF PAA levels.

Adult↗