Biomedical subjects

Takashi Asada

Publications and source records attributed to Takashi Asada.

At least 19 recordsLinked to original sources

PubMed2005

Activation of A1 and A2 noradrenergic neurons in response to running in the rat.

Since running accompanied with blood lactate accumulation stimulates the release of adrenocorticotropic hormone (ACTH), running above the lactate threshold (LT) acts as stress (running stress). To examine whether A1/A2 noradrenergic neurons that project to the hypothalamus activate under running stress, c-Fos immunohistochemistry was used to compare the effects of running with or without stress response on A1/A2 noradrenergic neurons. Blood lactate and plasma ACTH concentrations significantly increased in the running stress group, but not in the running without stress response and control groups, confirming different physiological impacts between different intensity of running with or without stress. Running stress markedly increased c-Fos accumulation in the A1/A2 noradrenergic neurons. Running without stress response also induced a significant increase in c-Fos expression in the A1/A2 noradrenergic neurons, and the percentage of the increase was smaller than that of running stress. The extent of c-Fos expression in the A1/A2 noradrenergic neurons correlates with exercise intensity, signifying that this neuronal activation is running speed-dependent. We thus suggest that A1/A2 noradrenergic neurons are activated in response to not only running stress, but also to other physiological running, enhanced by non-stressful running. These findings will be helpful in studies of specific neurocircuits and in identifying their functions in response to running at different intensities.

Adaptation, Physiological↗

PubMed2005

GABA(A) receptor gamma subunits in the hippocampus of the rat after perforant pathway lesion.

Immunohistochemical and Western blotting techniques were employed to examine the alterations in immunostaining of the gamma-amino butyric acid (GABA) receptor subunits gamma 1/3 and 2 within the hippocampus of the rat brain at 1, 3, 7, 14, and 30 days after a unilateral perforant pathway lesion. At 1, 3, and 7 days post-lesion, we observed a remarkable decrease in gamma 1/3 neuropil staining in the deafferented zone (i.e., the outer molecular layer of the dentate gyrus ipsilateral to the lesion), although at 3 and 7 days post-lesion, staining intensity was considerably recovered. At 14 days post-lesion, the gamma 1/3 immunostaining was indistinguishable from that of controls and it appeared yet more robust at 30 days post-lesion. We also observed a slight decrease in gamma 2 neuropil staining until 7 days post-lesion, and an increase in gamma 2 staining at 30 days post-lesion. Western blot analysis demonstrated data that was relatively consistent with our immunohistochemical observations, although gamma 3 was hardly detectable. Our study suggests that gamma subunits of the GABA(A) receptor in the dentate gyrus display a plastic response to the deafferentation of the perforant pathway.

Animals↗

PubMed2005

Determination of pesticides in compost by pressurized liquid extraction and gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric method was developed for the determination of pesticides in compost. The investigated pesticides included two fungicides, two herbicides and 10 insecticides. The pesticides were extracted from the compost by pressurized liquid extraction. The extract was cleaned up by a partition between hexane and acetonitrile followed by a dispersive solid-phase extraction using a porous carbon made from Moso bamboo (Phyllostachys pubescens). The overall recoveries were 81-104% and the relative standard deviations (RSDs) ranged from 2.4 to 12%. The minimum detectable concentrations were 0.02-0.04 microg g(-1). This method was successfully applied to a compost sample from food waste as well as commercial compost.

Chemical Fractionation↗

PubMed2005

Immunohistochemical study of the hnRNP A2 and B1 in the hippocampal formations of brains with Alzheimer's disease.

To elucidate the post-transcriptional regulation in the subjects with Alzheimer's disease (AD), we employed immunohistochemical techniques and examined the expression of the heterogeneous nuclear ribonucleoprotein (hnRNP) A2 and B1 in the hippocampus with neurofibrillary tangle (NFT) neuropathology. In the mildly affected subjects (Braak stages I and II), the most intense A2 immunoreactivity was observed in the CA3 to CA1 neurons. In the moderately (Braak stages III and IV) and severely affected subjects (Braak stages V and VI), the CA1 region demonstrated a decrease in the number of A2 immunoreactive neurons and in immunoreactivity in the remaining neurons, while within the CA4 to CA2 in the severely affected subjects, the majority of neurons showed increased A2 immunoreactivity. An intense B1 immunoreactivity was observed throughout the CA subfields. In the CA1 subfield of the moderately affected subjects and in the extensive hippocampal regions of the severely affected subjects, a decrease in B1 immunoreactivity was observed. Double-immunolabeling studies demonstrated that tangle-bearing neurons reduced A2 and B1 immunoreactivity. Our study suggests that hnRNP A2 and B1 display different responses in the AD hippocampus, and further suggests that the post-transcriptional regulation is disturbed in neurons of the AD hippocampus.

Aged↗

PubMed2005

The prediction of rapid conversion to Alzheimer's disease in mild cognitive impairment using regional cerebral blood flow SPECT.

Mild cognitive impairment (MCI) comprises a heterogeneous group with a variety of clinical outcomes and they are at risk for developing Alzheimer's disease (AD). The prediction of conversion from MCI to AD using the initial neuroimaging studies is an important research topic. We investigated the initial regional cerebral blood flow (rCBF) measurements using single photon emission computed tomography (SPECT) in individuals with 76 amnesic MCI (52 subjects converted to AD and 24 subjects did not convert to AD at 3-year follow-up) and 57 age- and gender-matched controls. We sought functional profiles associated with conversion to AD, then evaluated the predictive value of the initial rCBF SPECT. As compared with controls, AD converters demonstrated reduced blood flow in the bilateral parahippocampal gyri, precunei, posterior cingulate cortices, bilateral parietal association areas, and the right middle temporal gyrus. Non-converters also demonstrated significant reduction of rCBF in the posterior cingulated cortices and the right caudate nucleus when compared to controls. As compared with non-converters, converters showed reductions of rCBF in the bilateral temporo-parietal areas and the precunei. The logistic regression model revealed that reduced rCBF in the inferior parietal lobule, angular gyrus, and precunei has high predictive value and discriminative ability. Although a cross-validation study is needed to conclude the usefulness of rCBF SPECT for the prediction of AD conversion in individuals with MCI, our data suggest that the initial rCBF SPECT studies of individuals with MCI may be useful in predicting who will convert to AD in the near future.

Aged↗

PubMed2005

Clinical analyses of sighted patients with non-24-hour sleep-wake syndrome: a study of 57 consecutively diagnosed cases.

STUDY OBJECTIVES: The objective of this study was to clarify the clinical features of sighted patients with non-24-hour sleep-wake syndrome. DESIGN: Clinical analyses of consecutive patients suffering from non-24-hour sleep-wake syndrome. SETTING: The sleep disorders clinic at Kohnodai Hospital, National Center of Neurology and Psychiatry, Japan. PATIENTS: Fifty-seven patients who were diagnosed consecutively as having non-24-hour sleep-wake syndrome between 1991 and 2001 were included in the study. MEASUREMENTS AND RESULTS: The clinical features and sleep characteristics of the patients were analyzed. A semistructured psychiatric interview that included the criteria for Axis I or II disorders of Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised was conducted, and relationships between psychiatric problems and non-24-hour sleep-wake syndrome were analyzed. The patient cohort included 41 (72%) men and 16 (28%) women. The onset of non-24-hour sleep-wake syndrome had occurred during the teenage years in 63% of the cohort, and the mean ( +/-SD) period of the sleep-wake cycle was 24.9 +/- 0.4 hours (range 24.4-26.5 hours). The mean sleep length of the patients was 9.3 +/- 1.3 hours, and 44% of them had a sleep length of between 9 and 10 hours. Psychiatric disorders had preceded the onset of non-24-hour sleep-wake syndrome in 16 patients (28%); of the remaining 41 patients, 14 (34%) developed major depression after the onset of non-24-hour sleep-wake syndrome. CONCLUSIONS: These results represent the first detailed clinical review of a relatively large number of sighted patients with non-24-hour sleep-wake syndrome.

Adult↗

PubMed2005

Genetic association analyses of PHOX2B and ASCL1 in neuropsychiatric disorders: evidence for association of ASCL1 with Parkinson's disease.

We previously identified frequent deletion/insertion polymorphisms in the 20-alanine homopolymer stretch of PHOX2B (PMX2B), the gene for a transcription factor that plays important roles in the development of oculomotor nerves and catecholaminergic neurons and regulates the expression of both tyrosine hydroxylase and dopamine beta-hydroxylase genes. An association was detected between gene polymorphisms and overall schizophrenia, and more specifically, schizophrenia with ocular misalignment. These prior results implied the existence of other schizophrenia susceptibility genes that interact with PHOX2B to increase risk of the combined phenotype. ASCL1 was considered as a candidate interacting partner of PHOX2B, as ASCL1 is a transcription factor that co-regulates catecholamine-synthesizing enzymes with PHOX2B. The genetic contributions of PHOX2B and ASCL1 were examined separately, along with epistatic interactions with broader candidate phenotypes. These phenotypes included not only schizophrenia, but also bipolar affective disorder and Parkinson's disease (PD), each of which involve catecholaminergic function. The current case-control analyses detected nominal associations between polyglutamine length variations in ASCL1 and PD (P=0.018), but supported neither the previously observed weak association between PHOX2B and general schizophrenia, nor other gene-disease correlations. Logistic regression analysis revealed the effect of ASCL1 dominant x PHOX2B additive (P=0.008) as an epistatic gene-gene interaction increasing risk of PD. ASCL1 controls development of the locus coeruleus (LC), and accumulating evidence suggests that the LC confers protective effects against the dopaminergic neurodegeneration inherent in PD. The present genetic data may thus suggest that polyglutamine length polymorphisms in ASCL1 could influence predispositions to PD through the fine-tuning of LC integrity.

Adult↗

PubMed2005

Immunohistochemical and immunoblot analysis of gamma-aminobutyric acid B receptor in the prefrontal cortex of subjects with schizophrenia and bipolar disorder.

Immunohistochemical and immunoblot techniques were employed to examine the distribution and expression of GABA(B) receptors in the prefrontal cortex of postmortem subjects with schizophrenia and bipolar disorder. GABA(B)R1a/b immunoreactivity was observed in the neuronal soma and dendrites as well as in the neuropil in the control subjects. GABA(B)R1a/b immunolabeling in neurons from the subjects with schizophrenia and bipolar disorder was less intense than in those from the control subjects. In control subjects, the distribution of GABA(B)R2 immunoreactivity was found to be similar to that of GABA(B)R1a/b. GABA(B)R2 immunolabeling in neurons from the bipolar disorder group appeared less intense than that of the normal controls as well as that in schizophrenic groups. Immunoblot analysis demonstrated a significant decrease in GABA(B)R1a levels in schizophrenic subjects, while there was a significant decrease in GABA(B)R1a, GABA(B)R1b, and GABA(B)R2 levels in bipolar subjects compared with the controls. The present study suggests that the GABA(B) receptor is involved in the pathophysiology of schizophrenia and bipolar disorder, and further suggests that the patterns of changes in GABA(B) receptor subtypes are different between these two disorders.

Adult↗

PubMed2005

Voxel-based morphometry to discriminate early Alzheimer's disease from controls.

We assessed the accuracy of voxel-based morphometry (VBM) using a three-dimensional T1-weighted MRI in discriminating Alzheimer's disease (AD) in the very early stage of amnestic type of mild cognitive impairment and age-matched healthy controls. We randomly divided these subjects into two groups. The first group comprising 30 AD patients and 41 controls was used to identify the area with the most significant gray matter loss in patients compared to normal controls based on the voxel-based analysis of a group comparison. The second group comprising 31 patients and 41 controls was used to determine the discrimination accuracy of VBM. A Z-score map for a gray matter image of a subject was obtained by comparison with mean and standard deviation gray matter images of the controls for each voxel after anatomical standardization and voxel normalization to global mean using the following equation; Z-score=([control mean]-[individual value])/(control S.D.). Receiver operating characteristic curves for a Z-score in the bilateral medial temporal areas including the entorhinal cortex with the most significant loss in the first group showed a high discrimination accuracy of 87.8%. This result would open up a possibility for early diagnosis of AD using VBM.

Aged↗

PubMed2005

Changes in hippocampal GABABR1 subunit expression in Alzheimer's patients: association with Braak staging.

Alterations in the gamma-aminobutyric acid (GABA) neurotransmitter and receptor systems may contribute to vulnerability of hippocampal pyramidal neurons in Alzheimer's disease (AD). The present study examined the immunohistochemical localization and distribution of GABA(B) receptor R1 protein (GBR1) in the hippocampus of 16 aged subjects with a range of neurofibrillary tangle (NFT) pathology as defined by Braak staging (I-VI). GBR1 immunoreactivity (IR) was localized to the soma and processes of hippocampal pyramidal cells and some non-pyramidal interneurons. In control subjects (Braak I/II), the intensity of neuronal GBR1 immunostaining differed among hippocampal fields, being most prominent in the CA4 and CA3/2 fields, moderate in the CA1 field, and very light in the dentate gyrus. AD cases with moderate NFT pathology (Braak III/IV) were characterized by increased GBR1-IR, particularly in the CA4 and CA3/2 fields. In the CA1 field of the majority of AD cases, the numbers of GBR1-IR neurons were significantly reduced, despite the presence of Nissl-labeled neurons in this region. These data indicate that GBR1 expression changes with the progression of NFT in AD hippocampus. At the onset of hippocampal pathology, increased or stable expression of GBR1 could contribute to neuronal resistance to the disease process. Advanced hippocampal pathology appears to be associated with decreased neuronal GBR1 staining in the CA1 region, which precedes neuronal cell death. Thus, changes in hippocampal GBR1 may reflect alterations in the balance between excitatory and inhibitory neurotransmitter systems, which likely contributes to dysfunction of hippocampal circuitry in AD.

Adenosine Triphosphatases↗

PubMed2005

Association study of the chemokine, CXC motif, ligand 1 (CXCL1) gene with sporadic Alzheimer's disease in a Japanese population.

Inflammation is profoundly involved in the development of Alzheimer's disease (AD) and other neurodegenerative diseases. Chemokine, CXC motif, ligand 1 (CXCL1; or GRO1) is an inflammatory cytokine and appears to be implicated in the pathogenesis of AD. It is of interest and importance to see if the CXCL1 gene, mapped on chromosome 4q12-q13, has potential for conferring the predisposition to AD. Here we report on an association study of the CXCL1 gene with sporadic AD patients in a Japanese population; three single nucleotide polymorphisms (SNPs) in the CXCL1 locus were investigated in 103 AD patients and 130 healthy individuals. The results indicate that neither genotype frequencies nor allele frequencies of the examined SNPs attained statistical significance even after being stratified by the presence or absence of the Apolipoprotein E epsilon4 allele. Therefore, the data presented here suggests that the CXCL1 gene could not be associated with the susceptibility to AD in a Japanese population.

Aged↗

PubMed2005

Brain magnetic resonance imaging and single photon emission computerized tomography findings in a case of relapsing polychondritis showing cognitive impairment and personality changes.

A 57-year-old female with relapsing polychondritis (RP) showing CNS complications is described with reference to the MRI and SPECT findings. At the age of 56, the patient was diagnosed with RP based on her symptoms, which included bilateral auricular chondritis, nonerosive seronegative inflammatory polyarthritis, and ocular inflammation, as well as vestibular dysfunction. During the course of the disease, she suffered from aseptic meningitis accompanied by delirium, which was resolved by treatment with cyclophosphamide, in addition to prednisolone concurrent with the improvement of her physical condition. After the meningitis improved, she developed a number of cognitive impairments, including time disorientation, agraphia, acalculia, constitutional apraxia, and personality changes. Simultaneously, we observed, via SPECT, a decrease in cerebral blood flow (CBF) in several regions, including the bilateral frontal, lateral temporal, and parietal regions. This is the first study to report on the CNS manifestations of RP with reference to MRI and SPECT findings.

Brain Mapping↗

PubMed2005

EEG filtering based on blind source separation (BSS) for early detection of Alzheimer's disease.

OBJECTIVE: Development of an EEG preprocessing technique for improvement of detection of Alzheimer's disease (AD). The technique is based on filtering of EEG data using blind source separation (BSS) and projection of components which are possibly sensitive to cortical neuronal impairment found in early stages of AD. METHODS: Artifact-free 20s intervals of raw resting EEG recordings from 22 patients with Mild Cognitive Impairment (MCI) who later proceeded to AD and 38 age-matched normal controls were decomposed into spatio-temporally decorrelated components using BSS algorithm 'AMUSE'. Filtered EEG was obtained by back projection of components with the highest linear predictability. Relative power of filtered data in delta, theta, alpha 1, alpha 2, beta 1, and beta 2 bands were processed with Linear Discriminant Analysis (LDA). RESULTS: Preprocessing improved the percentage of correctly classified patients and controls computed with jack-knifing cross-validation from 59 to 73% and from 76 to 84%, correspondingly. CONCLUSIONS: The proposed approach can significantly improve the sensitivity and specificity of EEG based diagnosis. SIGNIFICANCE: Filtering based on BSS can improve the performance of the existing EEG approaches to early diagnosis of Alzheimer's disease. It may also have potential for improvement of EEG classification in other clinical areas or fundamental research. The developed method is quite general and flexible, allowing for various extensions and improvements.

Aged↗

PubMed2005

[Role of psychiatry in prevention of accidental falling in the aged].

The high incidence of falling among the psychogeriatric patients has recently been acknowledged. Elderly patients with depression and dementia, and long-term hospitalized schizophrenic patients are particularly prone to falling. By sustaining falling, these patients suffer from not only injuries including femoral neck fracture but also consequent fall-phobia. As the results, quality of life and the prognosis of psychiatric illnesses of the fallers are affected. In order to prevent fallings, we must pay attention to the prescribed drugs, nursing issues and environmental aspects of wards. Muscle strengthening exercises may be especially useful for the prevention of falls among long-term hospitalized schizophrenic patients.

Accidental Falls↗

PubMed2004

Genetic and expression analyses of FZD3 in schizophrenia.

BACKGROUND: Wnt signaling plays important roles in neurodevelopmental processes. Frizzled is a receptor of Wnt protein, and the Frizzled 3 (FZD3) gene was recently reported to be associated with schizophrenia. Our study attempted to confirm associations between FZD3 and schizophrenia in Japanese family and case-control samples. METHODS: Genetic associations were evaluated using family-based transmission tests (212 families, 643 subjects) and case--control analysis (540 schizophrenia patients, 540 control sample). Six single nucleotide polymorphisms (SNPs) on the FZD3 locus were genotyped, and levels of FZD3 mRNA expression in postmortem brains were examined. RESULTS: Neither family- nor population-based studies supported associations between FZD3 and schizophrenia. FZD3 expression was unaltered in schizophrenic brains. CONCLUSIONS: Although two prior studies have reported associations using limited numbers of SNPs on FZD3, our intensive study failed to support any major contribution of FZD3 to schizophrenia susceptibility.

Adult↗

PubMed2004

GABAA receptor gamma subunits in the prefrontal cortex of patients with schizophrenia and bipolar disorder.

Immunohistochemical and immunoblot techniques were employed in order to examine alterations of the GABAA receptor gamma subunits in the prefrontal cortex from postmortem subjects with schizophrenia and bipolar disorder. Immunohistochemically, gamma 1/3 immunolabeling in the neuronal soma in the prefrontal cortex from subjects with bipolar disorder was more intense than that of the controls and the subjects with schizophrenia. The intensity of gamma 1/3 immunolabeling of the schizophrenic subjects was comparable with that of the controls. Immunoblot analysis demonstrated a significant increase in the gamma 1 subunit in the bipolar subjects, whereas no remarkable difference was detected in the schizophrenic subjects. The present study suggests that the GABAA receptor gamma subunit is differentially involved in schizophrenia and bipolar disorder, and that the gamma subunit is up-regulated in the prefrontal cortex of subjects with bipolar disorder.

Adult↗

PubMed2004

Effects of partial volume correction on discrimination between very early Alzheimer's dementia and controls using brain perfusion SPECT.

We assessed the accuracy of brain perfusion single-photon emission computed tomography (SPECT) in discriminating between patients with probable Alzheimer's disease (AD) at the very early stage and age-matched controls before and after partial volume correction (PVC). Three-dimensional MRI was used for PVC. We randomly divided the subjects into two groups. The first group, comprising 30 patients and 30 healthy volunteers, was used to identify the brain area with the most significant decrease in regional cerebral blood flow (rCBF) in patients compared with normal controls based on the voxel-based analysis of a group comparison. The second group, comprising 31 patients and 31 healthy volunteers, was used to study the improvement in diagnostic accuracy provided by PVC. A Z score map for a SPECT image of a subject was obtained by comparison with mean and standard deviation SPECT images of the healthy volunteers for each voxel after anatomical standardization and voxel normalization to global mean or cerebellar values using the following equation: Z score = ([control mean]-[individual value] )/(control SD). Analysis of receiver operating characteristics curves for a Z score discriminating AD and controls in the posterior cingulate gyrus, where a significant decrease in rCBF was identified in the first group, showed that the PVC significantly enhanced the accuracy of the SPECT diagnosis of very early AD from 73.9% to 83.7% with global mean normalization. The PVC mildly enhanced the accuracy from 73.1% to 76.3% with cerebellar normalization. This result suggests that early diagnosis of AD requires PVC in a SPECT study.

Aged↗

PubMed2004

Association between tau polymorphism and male early-onset Alzheimer's disease.

Neurofibrillary tangles, containing hyperphosphorylated microtubule-associated protein tau, are one of the major pathological hallmarks of Alzheimer's disease. To investigate a possible association between tau genotypes and the risk of Alzheimer's disease, we screened for polymorphisms in the tau gene and found a novel polymorphism IVS11 + 90G --> A. A case-control study (874 patients and 678 controls) showed a significant association between possession of the A allele and male Alzheimer's disease with early-onset (age of onset before 65, odds ratio = 2.65; 95% confidence interval 1.30-5.42), suggesting that age and gender modify the risk effect. However, we failed to replicate the reported association between the Saitohin gene located in the tau intron 9 and Japanese Alzheimer's disease.

Adult↗