Search PubMed⌕ Search

Biomedical subjects

Shigetoshi Kuroda

Publications and source records attributed to Shigetoshi Kuroda.

At least 37 records · Page 2Linked to original sources
PubMed2004

Contrasting Fos expression induced by acute reboxetine and fluoxetine in the rat forebrain: neuroanatomical substrates for the antidepressant effect.

RATIONALE: Antidepressants preferentially facilitating serotonin seem to be particularly effective for treating the anxiety and aggressive component of the depressive syndrome, whereas those with a noradrenergic profile seem to be more effective in reducing psychomotor retardation, although their overall antidepressant effects are about the same. However, the mechanism of this difference remains unknown. OBJECTIVES: To investigate the neural substrate for the different therapeutic efficacies of fluoxetine and reboxetine, we examined the regional Fos immunoreactivity (Fos-ir) induced by the two agents. METHODS: Male Wistar rats (290-330 g) were given a subcutaneous injection of fluoxetine (5 or 10 mg/kg), reboxetine (5 or 10 mg/kg) or saline. Two hours later, rats were perfused through the ascending aorta and their brains were processed for Fos immunohistochemistry. Fos-ir was quantified by counting the number of Fos-ir-positive nuclei in six areas of the forebrain. RESULTS: The shell of the nucleus accumbens was the only region in which both fluoxetine and reboxetine equally increased Fos-ir expression. Fluoxetine particularly induced Fos-ir in the central nucleus of the amygdala. In contrast, reboxetine induced Fos-ir in the cingulate cortex area 3 and the lateral orbital cortex. CONCLUSIONS: These results suggest that the shell region may be one possible target for the antidepressant effects of fluoxetine and reboxetine. Furthermore, the difference in their clinical effects may depend on their different target sites of action.

Animals↗
PubMed2004

An autopsy case of hereditary diffuse leukoencephalopathy with spheroids, clinically suspected of Alzheimer's disease.

We report here a case of orthochromatic leukodystrophy with spheroids. A 40-year-old woman developed forgetfulness. About 1 year after the onset, clinical examination confirmed global intellectual deterioration with amnesia, spatiotemporal disorientation, and impairment of judgment. At age 43, she experienced tonic-clonic convulsions several times, and died of pneumonia at the age of 44. Alzheimer's disease was suspected clinically. Pathologically, there was severe diffuse demyelination of the deep white matter of the frontal, parietal and occipital lobes with relative preservation of the subcortical U fibers. In the central demyelinated areas, myelin loss was severe with diffuse gliosis, moderate loss of axons, and many axonal spheroids. At the periphery of the severely degenerated regions, there were a lot of macrophages and most had non-metachromatic lipid granules. The cerebral cortex was intact. The neuropathological findings of this case are consistent with hereditary diffuse leukoencephalopathy with spheroids (HDLS). Ten cases of HDLS were reviewed and presented many findings in common. The gray matter was intact and U fibers were well preserved in most cases. In white matter lesions, severe loss of myelin, moderate to severe axonal loss, much axonal swelling, and the presence of macrophages and hypertrophic astrocytes were common findings. In some cases with HDLS, dementia appeared without obvious neurological manifestations in the early stage. We should remember that some cases with HDLS show clinical symptoms similar to Alzheimer's disease, especially in the early stage.

Adult↗
PubMed2004

Effects of alpha-tocopherol on an animal model of tauopathies.

We have reported that transgenic (Tg) mice overexpressing human tau protein develop filamentous tau aggregates in the CNS. We overexpressed the smallest human tau isoform (T44) in the mouse CNS to model tauopathies. These tau Tg mice acquire age-dependent CNS pathologies, including insoluble, hyperphosphorylated tau and argyrophilic intraneuronal inclusions formed by tau-immunoreactive filaments. Therefore, these Tg mice are a model that can be exploited for drug discovery in studies that target amelioration of tau-induced neurodegeneration as well as for elucidating mechanisms of tau pathology in various neurodegenerative tauopathies. Oxidative stress has been implicated in the pathogenesis of various neurodegenerative diseases, including tauopathies, and many epidemiological, clinical, and basic studies have suggested the neuroprotective effects of vitamin E in neurodegenerative diseases. To elucidate the role of oxidative damage in the pathological mechanisms of these Tg mice, we fed them alpha-tocopherol, the major component of antioxidant vitamin E. Supplementation of alpha-tocopherol suppressed and/or delayed the development of tau pathology, which correlated with improvement in the health and attenuation of motor weakness in the Tg mice. These results suggest that oxidative damage is involved in the pathological mechanisms of the tau Tg mice and that treatment with antioxidative agents like alpha-tocopherol may prevent neurodegenerative tauopathies.

Animals↗
PubMed2004

Increased expression of neuronal cyclooxygenase-2 in the hippocampus in amyotrophic lateral sclerosis both with and without dementia.

The pathophysiological basis of cognitive dysfunction, including frontotemporal dementia (FTD), in patients with amyotrophic lateral sclerosis (ALS) and ALS with dementia (ALSD) remains unclear. On the other hand, increased expression of cyclooxygenase-2 (COX-2) in the spinal cord is thought to play a pivotal role in motor neuron degeneration in ALS. In this study, to assess the relationship between the neuronal COX-2 expression in the cerebrum, the formation of tau- and alpha-synuclein-negative but ubiquitin-positive neuronal inclusions (UPIs), and dementia in motor neuron disease (MND), we examined neuronal COX-2 immunoreactivity in the frontal cortex and hippocampus of patients with non-demented ALS without UPIs ( n=11), ALSD with UPIs ( n=6), and normal controls ( n=24) using a quantitative immunohistochemical technique. Neuronal COX-2 expression in all CA1-4 in the hippocampus was significantly up-regulated in the ALSD group, and, to lesser degree but significantly, in the ALS group. Neuronal COX-2 expression in the frontal cortex was also significantly up-regulated in the ALSD group but not in the ALS group. These findings suggest that (1) the frontal cortex and hippocampus of MND are involved in the same pathogenic process associated with COX-2 induction that has been observed in spinal anterior horn cells, (2) COX-2 induction in the cerebrum is a pathogenic process that can occur even in the absence of UPI formation in MND, and (3) COX-2 expression in the cerebrum may be associated with cognitive dysfunction in MND.

Aged↗
PubMed2004

No association between the insulin degrading enzyme gene and Alzheimer's disease in a Japanese population.

Susceptibility to Alzheimer's disease (AD) is thought to be regulated by multiple genetic factors. Recently, three independent studies have reported that loci on chromosome 10q are linked with AD, and the insulin degrading enzyme (IDE; MIM 146680) gene located on chromosome 10q23-q25; IDE is located close to the maker D10S583, which exhibits a maximum LOD score for late-onset AD. We examined seven polymorphisms in the IDE gene, the marker D10S583 in the 5' flanking region, and SNPs in introns 1, 3, 11, 20, 21, and 22 (rs#1999764, 1855915, 1970244, 538469, 551266, and 489517, respectively). Four SNPs in introns 3, 11, 20, and 22 did not exhibit any polymorphisms in the Japanese population that was studied. D10S583 and two SNPs in introns 1 and 21 did not exhibit a significant association with early- or late-onset AD. In addition, no associations were observed for subgroups of AD grouped according to APOE status. The present study indicates that the IDE gene polymorphisms do not confer susceptibility to early- or late-onset AD at least in a Japanese population.

Aged↗
PubMed2004

Association of the Neprilysin gene with susceptibility to late-onset Alzheimer's disease.

Neprilysin (NEP), also known as neutral endopeptidase, enkephalinase, CD 10, and common acute lymphoblastic leukemia antigen, is a 97-kD protein. NEP can degrade amyloid beta peptides, and its mRNA and protein levels are known to be reduced in the brains of patients with Alzheimer's disease (AD), making the NEP gene a substantial candidate for an AD risk factor. We examined the genetic association of three NEP polymorphisms, a GT-repeat polymorphism and two single nucleotide polymorphisms (SNPs, -1075A>G and -1284G>C) in its promoter region, with AD in a Japanese case-control sample (240 patients and 163 controls). The GT-repeat polymorphism, but not the SNPs, was significantly associated with late-onset AD (p = 0.0007). Our findings suggest that the GT-repeat polymorphism in the promoter region of the NEP gene or some other unknown polymorphisms, which are in a linkage disequilibrium, confer a susceptibility to late-onset AD.

Age of Onset↗
PubMed2004

Neuronal expression of cyclooxygenase-2, a pro-inflammatory protein, in the hippocampus of patients with schizophrenia.

Several types of evidence suggesting that the inflammatory response system is associated with pathophysiology of schizophrenia have been accumulated. Recently, a prospective double-blind study demonstrated that supplementary treatment with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, produced significantly greater improvement in scores on the Positive and Negative Syndrome Scale (PANSS) and on all subscales during the acute phase in patients with schizophrenia compared with risperidone alone therapy. The therapeutic effect of celecoxib on the psychopathology of schizophrenia is speculated to be based on COX activity inhibition; however, the detailed pharmacological mechanisms are unclear. To clarify whether or not COX-2 expression is altered in schizophrenia, we examined neuronal COX-2 expression in the hippocampus from cases of schizophrenia (n = 17), normal controls (n = 22), and cases of Alzheimer's disease (AD) as a positive control (n = 17). Quantitative immunohistochemical analysis demonstrated that neuronal COX-2 expression was significantly up-regulated in each CA1-4 region in Alzheimer's disease compared with controls, and that the mean COX-2 immunointensity in CA1-4 was significantly correlated with Abeta load in cases of Alzheimer's disease. In contrast, COX-2 expression was not up-regulated in any subdivision of the hippocampus in the schizophrenia group. These results suggest that celecoxib may affect the pathophysiology of schizophrenia through COX-2-independent actions rather than by inhibiting activity of up-regulated COX-2 protein.

Aged↗
PubMed2004

Autochthonous experience, heightened awareness, and perception distortion in patients with schizophrenia: a symptomatological study.

Early symptoms of schizophrenia' (ESS) proposed by Nakayasu, are present during schizophrenic prodromal periods. Some of these symptoms can continue after the florid manifestation of the disease and the patients often experience them with ego-alien feelings. Autochthonous experience, heightened awareness, and perception distortion (AHP) were selected from the list of ESS. The aim of this study was to confirm both prevalence and specificity of AHP in patients with schizophrenia as well as the relevance of the presence of AHP to symptomatology of schizophrenia. A structured interview was conducted to identify the presence of AHP in three groups of subjects; a schizophrenia group (Sc) with 37 patients, an affective disorder group (AD) with 27 patients, and a control group (NC) with 39 people. The prevalence of AHP was compared among the groups. Within the Sc, the relevance of AHP to Brief Psychiatric Rating Scale (BPRS) was assessed. AHP were present significantly more frequently in the Sc. The total scores for BPRS in the schizophrenic patients with AHP were significantly higher than in the patients without AHP. There was close correlation between AHP and BPRS items, with the degree of relevance depending on the form or perceptual domain. In conclusion, AHP were characteristic of patients with frank schizophrenia. To judge whether AHP were adequately specific to frank schizophrenia, further research of larger subjects is needed. Understanding the characteristics of AHP in patients with frank schizophrenia is important in the symptomatological evaluation of schizophrenia.

Adult↗
PubMed2004

Pick's disease pathology of a missense mutation of S305N of frontotemporal dementia and parkinsonism linked to chromosome 17: another phenotype of S305N.

We report the second phenotype of frontotemporal dementia and parkinsonism linked to chromosome 17 with S305N similar to Pick's disease pathology in two brothers. The brain of the older brother showed macroscopic atrophy compatible with Pick's disease, and subsequent tau gene analysis revealed heterozygous S305N mutation in exon 10 of the tau gene. Round-shaped neuronal inclusions similar to Pick's bodies were positive for phosphorylated serine 262 as well as other anti-tau antisera, which is different from immunoexpression of Pick's bodies. Ultrastructurally, these neuronal inclusions consisted of straight, randomly orientated fibrils measuring approximately 10-20 nm in width and 60-600 nm in length. This ultrastructural profile is similar to that of the first case of S305N. S305N reported here can cause another phenotype closely resembling Pick's disease.

Asparagine↗
PubMed2004

Characteristics and outcomes of school refusal in Hiroshima, Japan: proposals for network therapy.

The authors conducted a study on children undergoing treatment at major school refusal treatment centers in Hiroshima Prefecture. On the whole, school refusal in the prefecture was found to peak between 13 and 14 years of age. By age group, the main reason for school refusal in elementary school group was parent-child relationship with separation anxiety. Given additional problems such as neglect at home and complicated social situations in their schools, junior high school students were found to present diverse symptoms from introversion and self-analysis to extroversion, neglect of studies, and delinquency. Among high school students, there were more cases suffering withdrawal and schizophrenia spectrum disorders. The major task regarding treatment seems to lie in how to treat complex cases combining different problems. We summarized herein the studies we have carried out and propose a model for a network therapy system based on functional liaisons between treatment centers. With this system, a child psychiatric medical facility plays the part of a liaison center for the overall network system.

Absenteeism↗
PubMed2003

The human frizzled-3 (FZD3) gene on chromosome 8p21, a receptor gene for Wnt ligands, is associated with the susceptibility to schizophrenia.

Neurodevelopmental abnormalities have been reported in studies on the pathogenesis of schizophrenia. The Wnt-signaling pathway has been implicated in a variety of processes in neurodevelopment, and the frizzled proteins have been identified as receptors for Wnt ligands. Of the frizzled proteins, frizzled-3 (FZD3) is required for formation of the neural crest and for development of major fiber tracts in the CNS. The human FZD3 gene is located on chromosome 8p21, a positive linkage locus for schizophrenia. We analyzed polymorphisms of the FZD3 gene in patients with schizophrenia and control subjects in the Japanese population. We found a significant association between schizophrenia and the FZD3 gene in single nucleotide polymorphisms and haplotype analyses. Our data suggest that dysregulation of the Wnt-signaling pathway may be involved in the susceptibility to schizophrenia.

Adult↗
PubMed2003

No association between the sigma receptor type 1 gene and schizophrenia: results of analysis and meta-analysis of case-control studies.

BACKGROUND: Several lines of evidence have supported possible roles of the sigma receptors in the etiology of schizophrenia and mechanisms of antipsychotic efficacy. An association study provided genetic evidence that the sigma receptor type 1 gene (SIGMAR1) was a possible susceptibility factor for schizophrenia, however, it was not replicated by a subsequent study. It is necessary to evaluate further the possibility that the SIGMAR1 gene is associated with susceptibility to schizophrenia. METHODS: A case-control association study between two polymorphisms of the SIGMAR1 gene, G-241T/C-240T and Gln2Pro, and schizophrenia in Japanese population, and meta-analysis including present and previous studies. RESULTS: There was no significant association of any allele or genotype of the polymorphisms with schizophrenia. Neither significant association was observed with hebephrenic or paranoid subtype of schizophrenia. Furthermore, a meta-analysis including the present and previous studies comprising 779 controls and 636 schizophrenics also revealed no significant association between the SIGMAR1 gene and schizophrenia. CONCLUSION: In view of this evidence, it is likely that the SIGMAR1 gene does not confer susceptibility to schizophrenia.

Asian People↗
PubMed2003

No association between the dihydropyrimidinase-related protein 2 (DRP-2) gene and bipolar disorder in humans.

Several susceptibility loci for both of schizophrenia and bipolar disorder (BPD) have been found to overlap on several chromosomes including 8p21. Expression of dihydropyrimidinase-related protein 2 (DRP-2), which gene is located on 8p21, was found to be reduced in the brains of individuals with schizophrenia and BPD. Recently, we demonstrated a significant association between the DRP-2 gene and schizophrenia. Based on the rationale, we investigated the genetic association of the DRP-2 gene with BPD using a case-control study in the Japanese population. However, no significant associations were found between five polymorphisms of the DRP-2 gene (-975C>G, 352G>A, 426C>T, 1506T>C, and *2236T>C), and BPD, nor were associations detected between either of the polymorphisms and any subtype of BPD, bipolars I and II. The present study did not provide any evidence for a contribution of the DRP-2 gene to susceptibility to BPD.

Adult↗
PubMed2003

Variability and heterogeneity in Alzheimer's disease with cotton wool plaques: a clinicopathological study of four autopsy cases.

We describe three cases of early- (cases 1-3, 28-39 years) and one of late-onset (case 4, 76 years) Alzheimer's disease (AD) with 'cotton wool' plaques (CWPs) but without a family history indicating autosomal dominant inheritance. The early-onset cases, but not the late-onset case, showed remarkable aggression, disinhibition, and impulsiveness. Spastic paraparesis was observed in only one early-onset case. Hematoxylin-eosin-stained sections showed numerous CWPs, especially in the temporal cortex, in all cases. Bielschowsky-stained sections showed neurofibrillary tangles and minor neuritic changes surrounding the CWPs in three cases, but not in case 2. Gallyas-Braak-stained sections showed weak argyrophilia in homogeneous material of the CWPs in cases 2 and 4. Quantitative analysis demonstrated that Abeta42 was deposited more predominantly than Abeta40 in three cases. However, in case 2, approximately twice as much Abeta40 as Abeta42 was deposited. Tau immunostaining demonstrated neuritic changes in three cases, but not in case 2. alpha-Synuclein-positive Lewy bodies (LBs) and astrocytic lesions containing non-Abeta component of AD amyloid (NAC), a central fragment of alpha-synuclein, were found in case 3. In conclusion, (1) a frontal lobe syndrome-like personality change may be one of the characteristic clinical features of early-onset CWP-AD, (2) the deposition pattern of Abeta40 and Abeta42 in CWP-AD is more variable than that of presenilin-1-linked cases, (3) Abeta deposition can result in development of dementia without tau pathology, and (4) CWP-AD with LBs and several other neurodegenerative disorders with LBs share a common process involving alpha-synuclein and NAC deposition.

Adult↗
PubMed2003

Cyclooxygenase-2 in the hippocampus is up-regulated in Alzheimer's disease but not in variant Alzheimer's disease with cotton wool plaques in humans.

We examined neuronal expression of cyclooxygenase-2, a pro-inflammatory protein, and neuron densities in the CA1-4 of the hippocampus in three cases of Alzheimer's disease with cotton wool plaques (CWP-AD), 17 cases of typical Alzheimer's disease without CWPs (tAD), and 26 normal controls. Cyclooxygenase-2 expression was significantly increased in all of the CA1-4 in tAD, but not in any subdivision in CWP-AD, compared with controls. Cyclooxygenase-2 expression in tAD was also significantly up-regulated compared with that in CWP-AD in all subdivisions. Furthermore, neuron density in the hippocampus was not significantly reduced in CWP-AD cases compared with controls despite remarkable intra- and extraneuronal Abeta deposition. These findings suggest that unknown factors besides Abeta deposition are necessary for the cyclooxygenase-2 up-regulation and neurodegeneration in Alzheimer's disease.

Aged↗
PubMed2003

The human dihydropyrimidinase-related protein 2 gene on chromosome 8p21 is associated with paranoid-type schizophrenia.

BACKGROUND: The dihydropyrimidinase-related protein (DRP) family, also called the collapsin response mediator protein, is implicated in the developmental process of the nervous system. Dysfunction of DRPs may result in neurodevelopmental abnormalities, which may be a factor in the pathogenesis of schizophrenia. The expression of one member of DRP-2 in humans has been reported to be decreased in the brains of people with schizophrenia. In addition, the DRP-2 gene (Dihydropyrimidinase-like 2; DPYSL2) is located on chromosome 8p21, a region that has been implicated in schizophrenia in genetic linkage studies. METHODS: We investigated a genetic association between five polymorphisms of the DRP-2 gene and schizophrenia in the Japanese population. RESULTS: The *2236T>C polymorphism in the 3' untranslated region (3'UTR) exhibited significant differences with respect to the distribution of the genotype and allele in patients compared with control subjects. The frequency of the *2236C allele was significantly higher in control subjects than patients with schizophrenia (p =.0097) and paranoid-type schizophrenia (p =.0083). CONCLUSIONS: Our results suggest that the *2236C allele in the 3'UTR of the DRP-2 gene, or an unknown mutation in linkage disequilibrium with this allele, may reduce the susceptibility to schizophrenia, especially the paranoid subtype.

Alleles↗
PubMed2003

Association study of the brain-derived neurotrophic factor (BDNF) gene with bipolar disorder.

Brain-derived neurotrophic factor (BDNF) belongs to a family of neurotrophic factors and has been demonstrated to promote the survival, differentiation, and maintenance of a broad variety of central nervous system neurons. Several reports have suggested that the BDNF gene is a plausible functional candidate gene underlying the predisposition for developing bipolar disorder (BPD). In the present study, we investigated the possible role of the BDNF gene in the etiology of BPD using a matched case-control association design in a Japanese population. There was no evidence for an allelic or genotypic association of two polymorphisms (-1360C>T and 196G>A) of the BDNF gene with BPD. Furthermore, no significant association was observed between these polymorphisms and either of two diagnostic subtypes (bipolars I and II disorder). The results suggest that the BDNF gene is unlikely to confer susceptibility to BPD.

Bipolar Disorder↗