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M Nibuya

Publications and source records attributed to M Nibuya.

18 recordsLinked to original sources
PubMed1999

Repeated stress increases catalytic TrkB mRNA in rat hippocampus.

Northern blot analysis was utilized to distinguish between catalytic and truncated TrkB mRNA on the basis of transcript size. Repeated (10 days), but not acute, immobilization stress significantly increased levels of catalytic TrkB mRNA, but did not influence expression of truncated TrkB transcripts in rat hippocampus. Exposure to another paradigm, a combination of different, unpredictable stressors, also increased levels of catalytic, but not truncated, TrkB mRNA. In situ hybridization analysis demonstrated that chronic stress up-regulated TrkB mRNA in CA1 and CA3 pyramidal and dentate gyrus granule cells layers of hippocampus. As previously reported, both acute and chronic immobilization stress decreased expression of BDNF mRNA, suggesting that up-regulation of catalytic TrkB mRNA may be a compensatory adaptation to repeated stress.

Animals↗
PubMed1998

Transcriptional and translational regulation of phosphodiesterase type IV isozymes in rat brain by electroconvulsive seizure and antidepressant drug treatment.

We examined the influence of electroconvulsive seizure (ECS) and imipramine (IMI) treatment on the transcription and translation of cyclic nucleotide phosphodiesterase type IV (PDE IV) isozymes in the rat brain. Our in situ hybridization studies revealed an increase of PDE IV-B mRNA level in various brain regions after acute ECS. However, the increase of PDE IV activity was produced not by acute but by chronic ECS treatment in the frontal cortex. Increased PDE IV-B mRNA expression in frontal but not in hippocampal subfields was induced also after chronic ECS treatment. Although an increase in PDE IV-A mRNA expression of the dentate gyrus in the hippocampus was observed, no change of PDE IV activity was produced in the hippocampus by acute or chronic ECS treatment. These results suggest that the repeated increases of PDE IV-B mRNA expression are attributable to the increase of PDE IV translation. Increased PDE IV-B transcription and PDE IV translation in the frontal cortex were also produced after chronic IMI treatment. This is the first report demonstrating an expressional regulation of Drosophila melanogaster dunce (dnc) gene homologue PDE IV isozymes in the brain. Although no pathophysiological conditions with reduced PDE IV activity in the nervous system are known except for a learning deficit in the mutant fly dnc-, our results suggest possible treatments to cope with reduced PDE IV activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus.

The present study demonstrates that chronic, but not acute, adminstration of several different classes of antidepressants, including serotonin- and norepinephrine-selective reuptake inhibitors, increases the expression of cAMP response element binding protein (CREB) mRNA in rat hippocampus. In contrast, chronic administration of several nonantidepressant psychotropic drugs did not influence expression of CREB mRNA, demonstrating the pharmacological specificity of this effect. In situ hybridization analysis demonstrates that antidepressant administration increases expression of CREB mRNA in CA1 and CA3 pyramidal and dentate gyrus granule cell layers of the hippocampus. In addition, levels of CRE immunoreactivity and of CRE binding activity were increased by chronic antidepressant administration, which indicates that expression and function of CREB protein are increased along with its mRNA. Chronic administration of the phosphodiesterase (PDE) inhibitors rolipram or papaverine also increased expression of CREB mRNA in hippocampus, demonstrating a role for the cAMP cascade. Moreover, coadministration of rolipram with imipramine resulted in a more rapid induction of CREB than with either treatment alone. Increased expression and function of CREB suggest that specific target genes may be regulated by these treatments. We have found that levels of brain-derived neurotrophic factor (BDNF) and trkB mRNA are also increased by administration of antidepressants or PDE inhibitors. These findings indicate that upregulation of CREB is a common action of chronic antidepressant treatments that may lead to regulation of specific target genes, such as BDNF and trkB, and to the long-term effects of these treatments on brain function.

1-Naphthylamine↗
PubMed1996

Improvement of schizophrenic symptoms and changes in plasma HVA concentrations, plasma anti-D2 and anti-5-HT2 receptor activities with clozapine.

In order to investigate the biological mechanisms underlying the clinical efficacy of clozapine, 200 mg/day of clozapine was added to the drug regimens of 19 patients with chronic, anti-psychotic-resistant schizophrenia, and the plasma homovanillic acid (HVA), clozapine concentrations, anti-dopamine D2 and anti-serotonin 5-HT2 receptor activities were measured. After 28 days, six patients showed an improvement of more than 20% over baseline Brief Psychiatric Rating Scale (BPRS) scores. Mean plasma HVA concentrations and anti-D2 receptor activities did not change significantly in the entire group or in the six patients showing improvement. However, anti-5-HT2 receptor activities increased significantly in all 19 patients. Changes in BPRS scores did not correlate significantly with changes in plasma HVA or with changes in clozapine concentrations, or with anti-D2 and anti-5-HT2 receptor activities.

Adult↗
PubMed1996

Negative symptoms in nondeficit syndrome respond to neuroleptic treatment with changes in plasma homovanillic acid concentrations.

Deficit syndrome (DS) in schizophrenia is characterized by serious, chronic, and primary negative symptoms. We investigated differences in response to neuroleptic treatment between 8 DS patients and 6 nondeficit syndrome (NDS) patients who had the selective dopamine-D2 receptor blocker bromperidol added to their neuroleptic regimens. First, 9 mg/d was administered for 4 weeks, followed by 18 mg/d for another 4 weeks. Plasma homovanillic acid (pHVA) and plasma bromperidol concentrations were measured, and psychiatric symptoms were scored. In the NDS patients, both positive and negative symptoms improved. However, only the positive symptom scores changed in the DS patients. On day 4, pHVA concentrations of the NDS patients alone were significantly elevated. Plasma bromperidol concentrations did not differ between the groups. These results suggest that bromperidol exerts different effects on negative symptoms and pHVA concentrations between NDS and DS patients, effects that are unrelated to plasma bromperidol concentrations.

Adult↗
PubMed1995

Schizophrenic patients with deficit syndrome have higher plasma homovanillic acid concentrations and ventricular enlargement.

In order to investigate the biological characteristics of deficit syndrome in schizophrenia (Carpenter et al 1988), we examined cerebroventricular ratios (CVRs) and plasma concentrations of homovanillic acid (HVA) in a group of schizophrenic inpatients with deficit syndrome (n = 20) and in a control group of age- and sex-matched schizophrenic inpatients without deficit syndrome (n = 20). Symptoms and intelligence levels were measured using the Brief Psychiatric Rating Scale (BPRS) and the Wechsler Adult Intelligence Scale (WAIS), respectively. Patients in the deficit group had significantly higher CVRs as well as significantly elevated plasma HVA concentrations when compared with patients in the nondeficit group. We also found that the mean total WAIS score in the deficit group was significantly lower than that in the nondeficit group. These findings suggest the biological heterogeneity of schizophrenia. Increased central dopaminergic turnover, as indicated by higher plasma HVA concentrations, may partially account for the pathogenesis of deficit syndrome.

Adult↗
PubMed1995

Chronic antidepressant treatment down-regulates the induction of c-fos mRNA in response to acute stress in rat frontal cortex.

The present study examines the influence of electroconvulsive seizure (ECS), as well as several antidepressant drug treatments, on the induction of c-fos mRNA in response to acute restraint stress. Acute (45-minute) restraint stress resulted in five- to sixfold elevation of c-fos mRNA levels in rat frontal cortex. Chronic administration of ECS significantly decreased the induction of c-fos mRNA levels in response to acute restraint stress, and this effect was observed after chronic (6 to 9 days) but not acute (1 or 3 days) of ECS treatment. In addition, c-fos induction in response to acute restraint stress was down-regulated by chronic, but not acute, administration of tranylcypromine or imipramine, two drugs that nonselectively increase synaptic levels of norepinephrine and serotonin by inhibition of monoamine oxidase or neurotransmitter reuptake, respectively. Moreover, chronic administration of desipramine or sertraline, selective re-uptake inhibitors of norepinephrine, or serotonin, respectively, also significantly down-regulated the induction of c-fos mRNA in response to restraint stress. Chronic administration of ECS, tranylcypromine, or imipramine also decreased stressed-induced levels of NGFI-A mRNA, another immediate early gene transcription factor, whereas levels of c-jun mRNA were not influenced by either stress or antidepressant treatments. The results demonstrate that chronic, but not acute, administration of ECS and several different classes of antidepressant drugs down-regulates stress-induced levels of c-fos mRNA, suggesting that this effect may be a common, postreceptor action of antidepressant treatments.

1-Naphthylamine↗
PubMed1995

Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments.

The influence of chronic electroconvulsive seizure (ECS) or antidepressant drug treatments on expression of brain-derived neurotrophic factor (BDNF) and its receptor, trkB, was examined by in situ hybridization and Northern blot. In frontal cortex, acute ECS increased BDNF mRNA approximately twofold, an effect significantly augmented by a prior course of chronic ECS treatment (10 d). In the hippocampus, the influence of chronic ECS varied between the major subfields. In the dentate gyrus granule cell layer, chronic ECS decreased the acute induction of BDNF and trkB mRNA by approximately 50%, but prolonged their expression: levels remained elevated two- to threefold 18 hr later after the last chronic ECS treatment, but returned to control 18 hr after acute ECS. In CA3 and CA1 pyramidal cell layers, chronic ECS significantly elevated the acute induction of BDNF, and tended to prolong the expression of BDNF and trkB mRNA. A similar effect was observed in layer 2 of the piriform cortex, where chronic ECS significantly increased the acute induction and prolonged the expression of BDNF and trkB mRNA. Chronic (21 d), but not acute (1 d), administration of several different antidepressant drugs, including tranylcypromine, sertraline, desipramine, or mianserin, significantly increased BDNF mRNA and all but mianserin increased trkB mRNA in hippocampus. In contrast, chronic administration of nonantidepressant psychotropic drugs, including morphine, cocaine, or haloperidol, did not increase levels of BDNF mRNA. Furthermore, chronic administration of ECS or antidepressant drugs completely blocked the down-regulation of BDNF mRNA in the hippocampus in response to restraint stress. The enhanced induction and prolonged expression of BDNF in response to chronic ECS and antidepressant drug treatments could promote neuronal survival, and protect neurons from the damaging effects of stress.

Animals↗
PubMed1994

Longitudinal changes in symptoms and plasma homovanillic acid levels in chronically medicated schizophrenic patients.

A correlation has been noted between the changes in plasma homovanillic acid concentrations and changes in psychiatric symptoms induced by neuroleptic treatment. Our objective was to determine whether plasma homovanillic acid concentration changed in accordance with the changes in symptoms over time. Twenty-eight chronically medicated schizophrenic inpatients received the same treatment regimen for 1 year. Symptoms and plasma homovanillic acid concentrations were examined every month and whenever conditions deteriorated. Plasma homovanillic acid concentrations were significantly higher in the patients in the worst condition than in the patients in the best condition. Further, when comparing the best and worst conditions of both the positive and negative symptoms, the change in psychiatric rating of positive and negative symptoms was correlated significantly with the change in plasma homovanillic acid level. These results suggest that a change in plasma homovanillic acid concentration can be produced not only by neuroleptic-induced dopaminergic blocking but also by a change in positive and negative symptoms of schizophrenia.

Adult↗
PubMed1994

The first open study of zonisamide, a novel anticonvulsant, shows efficacy in mania.

1. Zonisamide, an anticonvulsant developed in Japan, is structurally similar to serotonin. Zonisamide has been proven to have a pharmacological profile that is very similar to that of carbamazepine. Thus, the effect of zonisamide was examined in 24 psychiatric patients: 15 with bipolar manic state, 6 with schizoaffective manic state, and 3 schizophrenic excitement. 2. Approximately 25% of all the patients and 33% of the bipolar manic patients showed remarkable global improvement with the addition of zonisamide. Approximately 71% of all the patients and 80% of the bipolar group had more than moderate global improvement. 3. No serious adverse reactions were found and no patients required zonisamide withdrawal. One patient developed both leukocytosis and mildly abnormal liver function test. One developed leukocytosis and another reported mild sleepiness. These reactions disappeared when zonisamide was discontinued.

Adult↗
PubMed1993

Interleukin-1 beta augments release of norepinephrine, dopamine, and serotonin in the rat anterior hypothalamus.

We investigated the effects of interleukin-1 beta (IL-1 beta), administered directly into the rat anterior hypothalamus (AHY), on monoamine release in the same region by using a brain microdialysis technique and an HPLC-electrochemical detection system. First, to study the local effects of IL-1 beta, we used a microdialysis probe equipped with a microinjection tube for administering IL-1 beta in the same region into which the probe had been inserted. IL-1 beta (1 ng) injected directly into the AHY elicited release of norepinephrine (NE), dopamine (DA), and 5-HT, as well as increases in their metabolites, 4-hydroxy-3-methoxyphenylglycol, 3,4-dihydroxyphenylacetic acid, 4-hydroxy-3-methoxyphenylacetic acid, and 5-hydroxyindole-3-acetic acid, in the AHY. Vehicle alone exerted no effect on monoamine release. Although the elevated levels of NE and DA persisted for more than 6 hr after injection of IL-1 beta, the elevated levels of 5-HT were transient. Second, in order to investigate whether this effect of IL-1 beta is a direct action in the AHY, we performed in vitro experiments using hypothalamus slices. IL-1 beta (0.1 and 1 nM) increased the levels of each monoamine released from hypothalamic slices in a dose-dependent manner. These findings suggest that IL-1 beta acts directly on the hypothalamus to induce release of NE, DA, and 5-HT. Third, the roles of prostaglandins (PGs) in NE release in the AHY elicited by direct injection of IL-1 beta were examined.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Plasma homovanillic acid, plasma anti-D1 and -D2 dopamine-receptor activity, and negative symptoms in chronically mediated schizophrenia.

We have investigated the relationship between the concentration of homovanillic acid in human plasma (pHVA) and plasma anti-D1 and anti-D2 dopamine receptor activity in chronic schizophrenic patients whose neuroleptic dosage was changed. The change in pHVA level correlated with that in anti-D1, not anti-D2 activity, thus suggesting that the neuroleptic-induced changes in pHVA concentration may be associated with the blocking of D1- as well as D2- receptors. The change of scores on the Scale for the Assessment of Negative Symptoms did not significantly correlate with changes in anti-D1 or anti-D2 activity, but did so correlated with the change in pHVA level.

Antipsychotic Agents↗
PubMed1992

Nortriptyline response in elderly depressed patients.

1. Depressed geriatric patients were treated with nortriptyline (NT) for 6 weeks. The authors measured serum levels of NT and 10-hydroxynortriptyline (10-OH-NT) using a column-switching HPLC method, and examined aging effects on NT steady-state levels to NT doses (doses/kg) ratios and NT levels to 10-OH-NT levels ratios as well as clinical response and propensity for side effects. 2. There was no significant relationship between the ages and the NT serum levels to NT doses (doses/kg) ratios, the ages and the 10-OH-NT levels to NT levels ratios, or the ages and the clinical response or the %improvement of Hamilton Scores. 3. Then the authors divided the subjects into two groups: a younger group and an elderly group with the cut off age of 60. The elderly group received significantly smaller doses of NT and had significantly lower serum levels of NT. The elderly group had tendency to have lower serum levels of 10-OH-NT. However, no significant difference was found in the improvement scores or the %improvement of depression. The elderly patients did not have higher propensity for unnegligible side effects.

Adult↗
PubMed1991

Serum interleukin-6 in schizophrenic patients.

We examined serum interleukin-6 (IL-6) in 90 schizophrenic patients in remission and 90 normal controls using enzyme-linked immuno-sorbent assay (ELISA). We found a significant difference in variation between the schizophrenic and the control groups (F = 10.9, P less than .002). The difference in distribution was also statistically significant by Kolmogorov-Smirnov (chi-square = 45.0, P less than .001). Eight patients had aberrantly high serum levels of interleukin-6. Since the higher levels of IL-6 are characteristically found in several autoimmune disorders, our finding suggests a link between schizophrenia and immune response, which could be either autoimmune or a process induced by reactivation of viruses.

Adolescent↗