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Biomedical subjects

Hisao Maeda

Publications and source records attributed to Hisao Maeda.

18 recordsLinked to original sources

The dopamine D1 receptor agonist, but not the D2 receptor agonist, induces gene expression of Homer 1a in rat striatum and nucleus accumbens.

Stimulation of dopamine receptors may induce striatal Homer 1a, an immediate-early gene (IEG) that is involved in the molecular mechanism for the signaling pathway of the group I metabotropic glutamate receptors. This study examined the effects of the agonists for dopamine D(1)-like and D(2)-like receptors on gene expression of Homer 1a, in comparison with the IEG c-fos expression, in the discrete brain regions of rats. The D(1)-like agonist SKF38393 (20 mg/kg, s.c.) significantly increased the mRNA levels of Homer 1a in the striatum and nucleus accumbens, but not in the medial prefrontal cortex or hippocampus, 2 h after injection, whereas the D(2)-like agonist quinpirole (1 mg/kg, s.c.) had no significant effect on Homer 1a mRNA levels in any brain region examined. Co-administration of SKF38393 and quinpirole significantly increased Homer 1a mRNA levels in the striatum, nucleus accumbens and hippocampus, while this effect was not significantly greater than that of SKF38393 alone. Any treatment did not affect the mRNA levels of other splicing variants, Homer 1b or 1c. In contrast, combination of both dopamine agonists produced a greater increase than SKF38393 did in the mRNA levels of c-fos in the nucleus accumbens, striatum and substantia nigra. These results suggest that stimulation of D(1)-like receptors, but not D(2)-like receptors, may induce gene expression of Homer 1a in the striatum and nucleus accumbens. However, in contrast to c-fos expression, it is unlikely that co-activation of both D(1)-like and D(2)-like receptors exerts a synergic action on Homer 1a expression in these regions.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Regulation of spinophilin Ser94 phosphorylation in neostriatal neurons involves both DARPP-32-dependent and independent pathways.

Spinophilin is a protein phosphatase-1 (PP-1)- and actin-binding protein that is enriched in dendritic spines. Phosphorylation of the actin-binding domain of rat spinophilin at one or more sites by protein kinase A (PKA) inhibits actin binding. Here, we investigated the regulation of mouse spinophilin that contains only a single PKA-site (Ser94) within its actin-binding domain. In vitro phosphorylation of Ser94 resulted in the dissociation of spinophilin from actin filaments. In mouse neostriatal slices, phospho-Ser94 (p-Ser94) was dephosphorylated mainly by PP-1 and also by PP-2A. Activation of dopamine D1 receptors in striatonigral medium spiny neurons, and of adenosine A 2A receptors in striatopallidal medium spiny neurons increased, whereas activation of dopamine D2 receptors in striatopallidal neurons decreased, spinophilin Ser94 phosphorylation. In neostriatal slices from DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of 32 kDa) knockout mice, the effects of D1, D2 and A 2A receptors were largely attenuated. Activation of NMDA receptors decreased Ser94 phosphorylation in a PP-2A-dependent, but DARPP-32-independent, manner. These results suggest that PKA-dependent phosphorylation of spinophilin at Ser94 in both striatonigral and striatopallidal neurons requires synergistic contributions from the PKA and DARPP-32/PP-1 pathways. In addition, PP-2A plays a role in Ser94 dephosphorylation in response to activation of both D2 and NMDA receptors.

Actins↗

Effect of zolpidem on sleep architecture and its next-morning residual effect in insomniac patients: a randomized crossover comparative study with brotizolam.

This study was conducted to determine the effect of zolpidem (ZOL) 10 mg orally on the sleep architecture and the next-morning residual effect in patients with non-organic insomnia (ICD-10) as compared to the effect of brotizolam (BTM) 0.25 mg orally, a widely used short-acting benzodiazepine (BZD) hypnotic in Japan, in a randomized, crossover comparative study. Fourteen patients with non-organic insomnia (3 males and 11 females; mean age of 54.9+/-S.D. 8.9 years). First three nights with placebo, middle three nights with either ZOL 10 mg or BTM 0.25 mg, and last three nights again with placebo in each session (a total of two sessions). Primary endpoints were polysomnography findings of sleep stages, sleep parameters, and sleep latency (SL) in the morning to examine calculable sleepiness as a residual effect. Secondary endpoint was sleep quality assessed by self-assessment questionnaire. At 150 min after Tmax, both ZOL and BTM significantly increased stage 2 (S2), and ZOL showed significantly longer slow wave sleep (SWS; stage 3+4) as compared to BTM. Stage wake was significantly increased by ZOL at the first withdrawal night and by BTM at the second withdrawal night. ZOL did not affect SL after rising, whereas BTM showed significantly shorter SL. Both drugs reduced the number of nocturnal awakenings and improved subjective sleep quality. The common adverse drug reaction (ADR) was sleepiness (3 patients) in each treatment. All events were mild. No serious adverse events occurred. ZOL is as effective as BTM in improving subjective sleep quality in patients with psychophysiological insomnia (PPI). ZOL has advantages over BTM in having a unique profile of increasing SWS with less next-morning residual effect.

Adult↗

An open study of risperidone liquid in the acute phase of schizophrenia.

An open-label study was performed to investigate the clinical efficacy and mechanisms of risperidone liquid in ameliorating positive symptoms in the acute phase of schizophrenia. Eighty-eight patients (M/F: 50/38; age: 18-74 years;, mean +/- SD =32 +/- 16 years) meeting DSM-IV criteria for schizophrenia and treated with risperidone liquid (14 patients also used lorazepam) were evaluated with regard to their clinical improvement and extrapyramidal side effects using the positive and negative syndrome scale (PANSS) and the Simpson and Angus scale (SAS), while plasma concentrations of HVA and MHPG were analysed by HPLC-ECD before and 4 weeks after risperidone liquid administration. Patients showing a 50% or greater improvement in PANSS scores were defined as responders. An improvement in the PANSS scores related to excitement, hostility and poor impulse control was seen within 7 days after administration of risperidone liquid, and an improvement with regard to hallucinatory behaviour and uncooperativeness was seen within 14 days after its administration. Finally, 68% of patients were classified as responders 4 weeks after risperidone liquid administration. The scores of SAS were not changed after risperidone liquid administration. Pretreatment plasma homovanillic acid (HVA) levels in the responders (8.1 +/- 2.9 ng/ml) were higher than those in nonresponders (5.9 +/- 1.9 ng/ml). In addition, a negative correlation was seen between the changes in plasma HVA levels and the percentage of improvement in PANSS scores. On the other hand, there were no differences between pretreatment plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and those of nonresponders. These results suggest that risperidone liquid is effective and well tolerated for the treatment of acute phase schizophrenic patients, and that efficacy is related to its affects on dopaminergic activity, not noradrenergic activity.

Acute Disease↗

Gender difference in QTc prolongation of people with mental disorders.

BACKGROUND: We examined gender difference in QTc interval distribution and its related factors in people with mental disorders. METHODS: We retrospectively reviewed medical charts of patients discharged from a university psychiatric unit between November 1997 and December 2000. Subjects were 328 patients (145 males and 183 females) taking psychotropics at their admission. We examined patient characteristics, medical history, diagnosis, and medication before admission. RESULTS: Mean QTc interval was 0.408 (SD = 0.036). QTc intervals in females were significantly longer than those in males. QTc of females without comorbidity was significantly longer than that of males. CONCLUSION: The influence of gender difference on QTc prolongation in people with mental disorders merits further research.

Journal Article↗

Recognition of facial expression and visual P300 in schizophrenic patients: differences between paranoid type patients and non-paranoid patients.

This study compared the effects of facial affective stimuli on visual event-related potentials (ERP) in schizophrenic patients and healthy subjects using photographs of babies depicting sadness (crying face), neutrality (neutral face), and pleasure (smiling face). Visual ERP were recorded using an oddball paradigm in 32 schizophrenic patients (16 paranoid type and 16 non-paranoid patients) and 32 age-matched healthy subjects. The P300 amplitude, latency, and the subject's reaction time were recorded. The P300 amplitude when viewing a photograph of a smiling baby was the smallest registered of three photographs for healthy subjects and paranoid type patients with successively greater amplitudes for neutrality and sadness. However, the P300 amplitude was the smallest while viewing crying photographs and was the largest while viewing a smiling photograph for non-paranoid patients. These results suggest that the P300 amplitude is influenced by viewing emotionally moving facial expressions and that the effect is different for different subtypes of schizophrenia. These differences may reflect differences in information processing resulted from emotional influences caused by visual-affective stimuli.

Adult↗

The nucleus accumbens unit activities related to the emotional significance of complex environmental stimuli in freely moving cats.

To establish the functional role of the nucleus accumbens (ACC) in emotionally motivated behaviors, extracellular single or multiple units were recorded from the ACC under an unanesthetized, freely moving non-operant condition in 43 cats. Then neuronal and behavioral responses to stimuli such as tones, live small animals, a human, air puffs and so on were analyzed using a videotape monitoring method. A total of 98 units were recorded from the ACC, and 34 (34.7%) of them responded to some of the stimuli. Of the 34 responded units, 5 (15%) units responded to quiet approach-provoking stimuli (appetitive stimuli), and 29 (85%) units responded to escape- or defensive attack-provoking stimuli (aversive stimuli). Although most of the units responded in an individual item-specific manner, there was no unit reacted to both the appetitive and aversive stimuli. The neuronal responses were not related to any movement or locomotion. The results were compared with those with the amygdala, and their neuronal responsiveness were shown to be quite different from each other. Although the ACC appears to be involved in the central processing of emotional behavior in some way, the role was suggested to be entirely different from that of the amygdala.

Action Potentials↗

Improvement of exploratory eye movements in schizophrenic patients during recovery period.

In the present paper exploratory eye movements were examined as biologic markers in both acute schizophrenic patients (acute patients discharged after approximately 3 months and treated as outpatients, n = 8; acute patients who were still in hospital after 6 months, n = 8) and chronic schizophrenic patients (hospital stay >5 years, n = 15) in comparison with age-matched healthy subjects (n = 30). Using an eye-mark recorder, exploratory eye movements were analyzed for mean gazing time (MGT), and total eye scanning length (TESL) as subjects viewed six simple pictures in preparation for copying them. In acute schizophrenic patients discharged after 6 months (DP), MGT became significantly shorter and TESL became longer after 3 or 6 months treatment. In acute schizophrenic patients during admission after 6 months, TESL became longer after 3 or 6 months of treatment. However, no significant changes were observed in chronic patients in these measures. In schizophrenic patients, negative symptom scores were positively correlated with MGT (r = 0.43; P < 0.001), and negatively correlated with TESL (r = -45; P < 0.001). These findings suggest that exploratory eye movements are a biologic state and trait marker useful for evaluation of schizophrenia.

Acute Disease↗

Study of image findings in rapid eye movement sleep behavioural disorder.

To elucidate the cause of idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), magnetic resonance imaging and single-photon emission computed tomography of the brain were conducted on 20 patients with RBD. Blood flow in the upper portion of both sides of the frontal lobe and pons was significantly lower in patients with RBD than in the normal elderly group. Among the patients with RBD, decreased blood flow in the frontal lobe showed no correlation with the extent of frontal lobe atrophy. Decreased blood flow in the upper portion of the frontal lobe and pons might be associated with the pathogenesis of idiopathic RBD.

Aged↗

Situation and problem of administration methods and the intermission of hypnotics.

The results of a questionnaire survey suggested four problems that might prolong the administration of benzodiazepine hypnotics without suspending the medication. First, psychiatrists did not actively consider the necessity of suspension of medication with hypnotics. Second, the period between improvement of insomnia and initiation of dose reduction was long, whereas the period between initiation of dose reduction and discontinuation was short. Third, to suspend medication of a hypnotic, every-other-day administration was used for the very short-acting and short-acting types, and substitution of the intermediate-acting or long-action type for the drugs with a short half-life were performed frequently. Finally, dose reduction and intermission of medication induced rebound insomnia, withdrawal symptoms, and recurrence of insomnia.

Adult↗

Decreased blood flow of the left thalamus during somnolent episodes in a case of recurrent hypersomnia.

A 24-year-old male with recurrent hypersomnia associated with decreased blood flow in the thalamus on single photon emission computed tomography (SPECT) is reported. In the hypersomnolent period, the decrease of blood flow in the left thalamus was revealed in the SPECT and slow waves appeared sporadically or sometimes as a burst on the electroencephalogram (EEG). In a phase of insomnia in the convalescent period there were almost no slow waves in the resting EEG but many slow waves appeared on hyperventilation EEG and the power spectrum at this hyperventilation resembled the power spectrum at the resting EEG in the hypersomnolent period. In the remission period there was no abnormal data in these testings.

Adult↗

Effects of aroma on sleep and biological rhythms.

The polysomnogram (PSG), blood melatonin concentration, rectal temperature, and answers to a self-evaluation questionnaire about the effects of agarwood (jinkoh in Japanese), which has been reported to have sleep-promoting effects were examined. The subjects tested were male medical students, who were free of otorhinolaryngological diseases and were non-smokers. The results of sleep stage and other sleep variables, and those of rectal temperature rhythm and blood melatonin concentrations showed no significant differences between the baseline nights, experimental nights, and recovery nights.

Adult↗

Case of head banging that continued to adolescence.

Head banging is a rhythmic movement disorder (RMD) along with headrolling and bodyrolling. The average age of onset is 9 months, and by 10 years of age the majority of subjects no longer complain of head banging. A case of head banging in which the symptoms continued to adolescence is reported. The RMD involved the patient abnormally rolling his body or head and hitting his head on walls during sleep. His head bangings were observed during sleep stage 2 and REM sleep. Doses of clonazepam ranging from 0.5 mg to 2 mg were administered for the RMD, which diminished when treated with 2 mg of clonazepam.

Adolescent↗

Neurotensin regulates DARPP-32 thr34 phosphorylation in neostriatal neurons by activation of dopamine D1-type receptors.

Neurotensin modulates dopaminergic transmission in the nigrostriatal system. DARPP-32, a dopamine- and cAMP-regulated phosphoprotein of Mr 32 kDa, is phosphorylated on Thr34 by cAMP-dependent protein kinase, resulting in its conversion into a potent inhibitor of protein phosphatase-1 (PP 1). Here, we examined the effect of neurotensin on DARPP-32 Thr34 phosphorylation using mouse neostriatal slices. Neurotensin stimulated DARPP-32 Thr34 phosphorylation by 4-7-fold with a K(0.5) of approximately 50 nM. The effect of neurotensin was antagonized by a combined neurotensin receptor type-1 (NTR1)/type-2 (NTR2) antagonist, SR142948. It was not antagonized by a NTR1 antagonist, SR48692 or by a NTR2 antagonist, levocabastine; neither was it antagonized by the two combined. Pretreatment with TTX or cobalt abolished the effect of neurotensin. The effect of neurotensin was antagonized by a dopamine D1 antagonist, SCH23390, and by ionotropic glutamate receptor antagonists, MK801 and CNQX. These results indicate that neurotensin stimulates the release of dopamine from nigrostriatal presynaptic terminals in an NMDA receptor- and AMPA receptor-dependent manner, leading to the increase in DARPP-32 Thr34 phosphorylation. Neurotensin stimulated the phosphorylation of Ser845 of the AMPA receptor GluR1 subunit in wild-type mice but not in DARPP-32 knockout mice. Thus, neurotensin, by stimulating the release of dopamine, activates the dopamine D1-receptor/cAMP/PKA/DARPP-32/PP 1 cascade.

Animals↗

Comparative study of short-term anxiolytic potency of alprazolam and tandospirone in psychiatric outpatients with anxiety disorders.

Anxiolytic potency of 1 week of treatment with alprazolam or tandospirone in psychiatric outpatients with anxiety disorders was evaluated by changes in the scores on the Hamilton Anxiety Scale and the State and Trait Anxiety Inventory and in the saliva level of free-3-methoxy-4-hydroxyphenylglycol (free-MHPG). Saliva level of free-MHPG was significantly reduced by 1 week of treatment with alprazolam but not with tandospirone. Reductions in the HAS score after 1 week of drug treatment were greater in patients treated with alprazolam than in those treated with tandospirone. These results indicate that the short-term anxiolytic potency of alprazolam is greater than that of tandospirone and that the saliva level of MHPG would be a useful marker for the evaluation of the therapeutic potency of anxiolytic agents. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗