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N Takei

Publications and source records attributed to N Takei.

At least 37 records · Page 2Linked to original sources
PubMed2001

N-methyl-D-aspartate-induced alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor down-regulation involves interaction of the carboxyl terminus of GluR2/3 with Pick1. Ligand-binding studies using Sindbis vectors carrying AMPA receptor decoys.

The dynamics of alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA)-type glutamate receptors, as represented by their exocytosis, endocytosis and cytoskeletal linkage, has often been implicated in N-methyl-d-aspartate (NMDA)-dependent synaptic plasticity. To explore the molecular mechanisms underlying the AMPA receptor dynamics, cultured hippocampal neurons were stimulated with 100 microm NMDA, and the biochemical and pharmacological changes in the ligand binding activity of AMPA receptor complexes and its subunits, GluR1 and GluR2/3, were investigated. The NMDA treatment reduced the total amount of bound [(3)H]AMPA on the surface of the neurons but not in their total membrane fraction. This process was mimicked by a protein kinase C activator, phorbol ester, but blocked by an inhibitor of the same kinase, calphostin C. The NMDA-induced down-regulation of the ligand binding activity was also reflected by the decreased AMPA-triggered channel activity as well as by the cells' reduced immunoreactivity for GluR1. In parallel, the NMDA treatment markedly altered the interaction between the AMPA receptor subunits and their associating molecule(s); the association of PDZ molecules, including Pick1, with GluR2/3 was enhanced in a protein-kinase-C-dependent manner. Viral expression vectors carrying GluR1 and GluR2 C-terminal decoys, both fused to enhanced green fluorescent protein, were transfected into hippocampal neurons to disrupt their interactions. The overexpression of the C-terminal decoy for GluR2 specifically and significantly blocked the NMDA-triggered reduction in [(3)H]AMPA binding, whereas that for GluR1 had no effects. Co-immunoprecipitation using anti-Pick1 antibodies revealed that the overexpressed GluR2 C-terminal decoy indeed prevented Pick1 from interacting with the endogenous GluR2/3. Therefore, these observations suggest that the NMDA-induced down-regulation of the functional AMPA receptors involves the interaction between GluR2/3 subunits and Pick1.

Animals↗
PubMed2001

Biological characterization and optical imaging of brain-derived neurotrophic factor-green fluorescent protein suggest an activity-dependent local release of brain-derived neurotrophic factor in neurites of cultured hippocampal neurons.

To visualize the release dynamics of the brain-derived neurotrophic factor (BDNF) involved in neural plasticity, we constructed a plasmid encoding green fluorescent protein (GFP) fused with BDNF. First, several biological studies confirmed that this fusion protein (BDNF-GFP) mimics the biological functions and the release kinetics of unfused (native) BDNF. Second, when BDNF-GFP was expressed in cultured hippocampal neurons, we observed that this protein formed striking clusters in the neurites of mature neurons and colocalized with the PSD-95 immunoreactivity. Such a clustered BDNF-GFP rapidly disappeared in response to depolarization with KCl, as revealed by confocal microscopic studies. These data suggest that BDNF is locally and rapidly released at synaptic sites in an activity-dependent manner. Optical studies using BDNF-GFP may provide important evidence regarding the participation of BDNF in synaptic plasticity.

Animals↗
PubMed2001

Cholesteryl ester transfer protein polymorphism associated with macroangiopathy in Japanese patients with type 2 diabetes.

A polymorphism in the gene for cholesteryl ester transfer protein (CETP) has been reported to be associated with serum cholesterol levels and risk for atherosclerotic vascular diseases, and to clarify the relationship between the gene polymorphism for CETP and macroangiopathy in diabetes mellitus, a cross-sectional study was performed. The subjects of the study were182 Japanese (age: 59.6+/-8.6 years) with type 2 diabetes and no signs of renal dysfunction, 24 of whom had macroangiopathy, and 158 of whom did not. The genotype of the subjects for the TaqIB polymorphism of CETP in intron one was analyzed by using polymerase chain reaction - restriction fragment length polymorphism. Serum CETP levels were significantly higher in the B1/B1 genotype than in the other genotypes (P<0.05). The serum CETP levels were correlated with the serum LDL cholesterol levels (P<0.01), but not with the HDL cholesterol levels. Macroangiopathy was more frequently observed in subjects with the B1/B1 genotype than in the other genotypes (odds ratio=2.953, 95% confidence interval=1.250-6.977, P=0.0136). Logistic regression analysis revealed that the CETP genotype was independently associated with macroangiopathy. The exact mechanism underlying the association remains unknown, but differences in serum CETP levels may be involved.

Aged↗
PubMed2001

BDNF as an anterophin; a novel neurotrophic relationship between brain neurons.

Studies of the peripheral nervous system have led to the concept of target-derived neurotrophic support. Neurotrophic factors such as nerve growth factor are now known to act as retrograde trophic factors--retrophins--that are produced in the target cells and released to presynaptic neurons. However, using brain-derived neurotrophic factor (BDNF) tagged with green-fluorescent protein to monitor the subcellular dynamics of BDNF in neurites, Tsumoto and colleagues have provided persuasive visual evidence that BDNF can be released at the synapses of brain neurons in an activity-dependent manner to act on postsynaptic neurons. Accordingly, BDNF serves as an anterophin to regulate postsynaptic development and plasticity in the central nervous system.

Animals↗
PubMed2001

FK506 facilitates chemical kindling induced by pentylenetetrazole in rats.

To clarify the possible role played by calcineurin in kindling development, we examined the effects of pretreatment with FK506, a selective calcineurin inhibitor, on pentylenetetrazole (PTZ) kindling in rats. FK506 facilitated the speed of kindling induced by repeated administration of 30-mg/kg PTZ, while FK506 did not ameliorate acute seizure manifestations after a single injection of PTZ. Our results suggested that calcineurin might exert an inhibitory effect on PTZ kindling.

Animals↗
PubMed2001

The association between obstetric complications and childhood-onset schizophrenia: a replication study.

BACKGROUND: Many previous studies have shown that individuals who develop schizophrenia in adult life are more likely than normal controls to have a history of obstetric complications (OCs) at birth. However, little attention has been paid to the involvement of OCs in the risk of developing childhood-onset schizophrenia (COS). In our earlier report, we found an association between OCs and the development of COS. In this study, we determined whether the association could be replicated in another, independent set of patients with COS. METHODS: OCs, birth weight and gestational age were retrospectively assessed in 35 children, aged between 14 and 15 years old (average 15.4 years), who met the DSM-III-R criteria for schizophrenia, and in age- and gender-matched controls (children with anxiety disorders). RESULTS: The COS patients showed significantly greater scores in all of the three measures of OCs according to the Parnas et al. scale compared to controls. Moreover, individuals exposed to OCs were about 3.2 times (odds ratio = 3.22; 95% confidence interval, 1.1-9.8) more likely to develop schizophrenia than those without a history of OCs. The mean birth weight was significantly lower in schizophrenics than in controls (P < 005). The frequency of prematurity signs with weight < 2500 g was significantly higher in schizophrenics than in controls (P < 0.05). CONCLUSION: Repeatedly reported association between OCs and adult-onset schizophrenia have also been demonstrated in patients with COS. This suggests that there may be a continuity between childhood- and adult-onset schizophrenia.

Adolescent↗
PubMed2001

Differences of symptoms and standardized weight index between patients with early-onset and late-onset anorexia nervosa.

OBJECTIVE: There have so far been no studies that directly compared clinical features between patients with early- and late-onset anorexia nervosa (AN). METHOD: We identified 64 patients with DSM-III-R AN. We defined individuals as an early-onset group, who had an age of onset before 14 years (N = 31), and the remaining as a late-onset group (N = 33). The clinical symptoms, body weight and weight index, were compared between the two groups. Subjects were dichotomized into those with extremely low weight and those remaining. We compared the proportion of the patients with extremely low weight between the two groups. RESULTS: The rates of 'self-induced vomiting' and 'purging' were significantly lower in a group of patients with early-onset AN than in those with late-onset AN. There were significantly fewer subjects with extremely low weight in early-onset than in late-onset AN group. CONCLUSION: We found clear differences in clinical features between early- and late-onset AN groups.

Adolescent↗
PubMed2001

The effects of dentate granule cell destruction on behavioural activity and Fos protein expression induced by systemic methamphetamine in rats.

1. We destroyed dentate granule cells unilaterally or bilaterally by means of intrahippocampal injection of colchicine in rats. Subsequently, we observed behavioural changes following the intraperitoneal injection of 2 mg kg(-1) methamphetamine or saline, in addition to quantitatively assessing Fos protein expression in several brain regions, including the medial prefrontal cortex, cingulate cortex, piriform cortex, dorsal striatum, and nucleus accumbens. 2. Bilaterally lesioned animals, when administered saline, showed a marked increase in locomotor activity compared with those of non-lesioned animals. With respect to the methamphetamine response, bilateral destruction resulted in a marked enhancement of locomotor activity, while the unilateral destruction led to a marked increase in rotation predominantly contralateral to the lesioned side, with no identifiable change in locomotor activity. 3. Bilaterally lesioned animals, when administered saline and having undergone an immunohistological examination, showed a marked increase in Fos expression in both sides of the nucleus accumbens. Bilaterally lesioned animals administered methamphetamine showed a marked increase in Fos expression in the right and left sides of all regions tested. Unilaterally lesioned animals administered methamphetamine showed a significant and bilateral enhancement in Fos expression in the medial prefrontal and cingulate cortices, and a marked and unilateral (ipsilateral to the lesioned side) enhancement of Fos protein in the piriform cortex, dorsal striatum, and nucleus accumbens. 4. The present findings suggest that dentate granule cells regulate methamphetamine-associated behavioural changes through the function of widespread areas of the brain, mostly the nucleus accumbens.

Animals↗
PubMed2001

Brain-derived neurotrophic factor enhances depolarization-evoked glutamate release in cultured cortical neurons.

Brain-derived neurotrophic factor (BDNF) has been reported to play an important role in neuronal plasticity. In this study, we examined the effect of BDNF on an activity-dependent synaptic function in an acute phase. First, we found that short-term treatment (10 min) with BDNF enhanced depolarization-evoked glutamate release in cultured cortical neurons. The enhancement diminished gradually according to the length of BDNF treatment. The BDNF-enhanced release did not require the synthesis of protein and mRNA. Both tetanus toxin and bafilomycin abolished the depolarization-evoked glutamate release with or without BDNF, indicating that BDNF acted via an exocytotic pathway. Next, we investigated the effect of BDNF on intracellular Ca(2+). BDNF potentiated the increase in intracellular Ca(2+) induced by depolarization. The Ca(2+) was derived from intracellular stores, because thapsigargin completely inhibited the potentiation. Furthermore, both thapsigargin and xestospongin C inhibited the effect of BDNF. These results suggested that the release of Ca(2+) from intracellular stores mediated by the IP(3) receptor was involved in the BDNF-enhanced glutamate release. Last, it was revealed that the enhancement of glutamate release by BDNF was dependent on the TrkB-PLC-gamma pathway. These results clearly demonstrate that short-term treatment with BDNF enhances an exocytotic pathway by potentiating the accumulation of intracellular Ca(2+) through intracellular stores.

Animals↗
PubMed2001

Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET.

OBJECTIVE: A positron emission tomography (PET) study has suggested that dopamine transporter density of the caudate/putamen is reduced in methamphetamine users. The authors measured nucleus accumbens and prefrontal cortex density, in addition to caudate/putamen density, in methamphetamine users and assessed the relation of these measures to the subjects' clinical characteristics. METHOD: PET and 2-beta-carbomethoxy-3beta-(4-[(11)C] fluorophenyl)tropane, a dopamine transporter ligand, were used to measure dopamine transporter density in 11 male methamphetamine users and nine male comparison subjects who did not use methamphetamine. Psychiatric symptoms in methamphetamine users were evaluated by using the Brief Psychiatric Rating Scale and applying a craving score. RESULTS: The dopamine transporter density in all three of the regions observed was significantly lower in the methamphetamine users than the comparison subjects. The severity of psychiatric symptoms was significantly correlated with the duration of methamphetamine use. The dopamine transporter reduction in the caudate/putamen and nucleus accumbens was significantly associated with the duration of methamphetamine use and closely related to the severity of persistent psychiatric symptoms. CONCLUSIONS: These findings suggest that longer use of methamphetamine may cause more severe psychiatric symptoms and greater reduction of dopamine transporter density in the brain. They also show that the dopamine transporter reduction may be long-lasting, even if methamphetamine use ceases. Further, persistent psychiatric symptoms in methamphetamine users, including psychotic symptoms, may be attributable to the reduction of dopamine transporter density.

Adult↗
PubMed2000

Predictive variables of interictal psychosis in epilepsy.

OBJECTIVE: To evaluate which variables predict interictal psychosis in epilepsy. METHODS: The authors reviewed the biological backgrounds, clinical characteristics, and EEG findings in 246 patients with epilepsy and interictal psychosis and in 658 control patients with epilepsy and no psychotic history. With a logistic regression approach, the significance of each variable for the development of interictal psychosis was evaluated. RESULTS: There are significant differences in family history of psychosis, age at onset of epilepsy, type of epilepsy, lateralization of epileptiform discharges, and level of intelligence between patients with interictal psychosis and those without it. Subsequent logistic regression analysis with all variables demonstrated that family history of psychosis, age at onset of epilepsy, type of seizures, and level of intelligence significantly correlated with psychosis. CONCLUSIONS: A family history of psychosis, earlier age at onset of epilepsy, complex partial seizures or generalized tonic clonic seizures, and borderline intellectual functioning were the most important predictors for development of interictal psychosis.

Adolescent↗
PubMed2000

A magnetic resonance imaging study of corpus callosum size in familial schizophrenic subjects, their relatives, and normal controls.

The corpus callosum is one of several brain regions thought to be abnormal in schizophrenia. We sought to investigate whether the size of the corpus callosum would be abnormally small in schizophrenic subjects from families with familial schizophrenia and their healthy relatives. We wished to determine whether an abnormal corpus callosum size is found in healthy relatives who are genetically at a greater risk than normal of developing or transmitting the disorder. Twenty-seven familial schizophrenics, 53 of their healthy first-degree relatives, and 35 normal volunteers underwent MRI brain scans. We defined 11 of the relatives as presumed 'obligate carriers', i.e. an individual who appears to be transmitting the schizophrenic gene(s). The mid-sagittal slice of the corpus callosum and the whole brain volume were measured blind to diagnostic and family group. We found no difference between schizophrenics, their relatives, and normal controls in the mid-sagittal area of the corpus callosum. There remained no difference when the relatives were divided into two groups comprising presumed 'obligate carriers' and 'non-obligate carriers'. Adjusting for age and whole brain area made no difference to the results. Families with several schizophrenic members are not associated with abnormality in the size of the corpus callosum.

Adult↗
PubMed2000

Premorbid IQ in patients with functional psychosis and their first-degree relatives.

Numerous studies have found deficits in premorbid IQ in schizophrenic patients, but it is not clear whether this deficit is shared by (a) patients with other functional psychoses, and (b) relatives of these patients. Ninety-one schizophrenic patients, 66 affective psychotic patients (29 schizoaffective and 37 manic or depressed), and 50 normal control subjects were administered the National Adult Reading Test (NART) which provides an estimate of premorbid IQ. The NART was also completed by 85 first-degree relatives of schizophrenic patients and by 65 first-degree relatives of affective psychotic patients. After adjustments were made for sex, social class, ethnicity and years of education, schizophrenic patients had significantly lower premorbid IQ than their relatives, the affective psychotic patients and controls. Manic and depressed patients had significantly lower NART scores than their first-degree relatives, but schizoaffective patients did not, and neither group differed significantly from controls. There was no significant difference in premorbid IQ between patients who had experienced obstetric complications (OC+) and those who had not (OC-). Both OC+ and OC- schizophrenic patients differed significantly from their relatives, but the disparity was greatest between OC+ patients and their relatives. Relatives of OC+ schizophrenic patients had significantly higher IQ than relatives of OC- schizophrenic patients.

Adult↗
PubMed2000

Mesencephalic neural stem (progenitor) cells develop to dopaminergic neurons more strongly in dopamine-depleted striatum than in intact striatum.

Epidermal growth factor (EGF)/fibroblast growth factor (FGF)-responsive stem (progenitor) cells from embryonic brain have self-renewing and multipotent properties and thus are good candidates for donor cells in neural transplantation. However, the survival and differentiation to mature neurons after grafting of stem cells into adult brain are rather poor. We hypothesize that the differentiation of stem cells to mature neurons, such as dopaminergic (DAergic) neurons, is dependent on environmental cues that control the ontogenic development. We compared the survival and differentiation between mesencephalic (MS) and cortical (CTx) stem (progenitor) cells, following grafting into bilateral striata of hemiparkinsonian model rats. MS and CTx stem cells were prepared from E12 rats and proliferated in serum-free medium with EGF or basic FGF for 2 weeks. One day after being primed to differentiate, the cell suspensions of both origins were grafted into the bilateral striata of adult rats that had unilateral 6-OHDA lesions in the substantia nigra. MS cells differentiated to tyrosine hydroxylase (TH)-positive neurons more strongly in DA-depleted striatum than in intact striatum, and methamphetamine-induced rotation was ameliorated in half of the grafted animals. Rosette-like cell aggregation and dysfunction of the blood-brain barrier (BBB) were less in and around the grafts in DA-depleted striatum, suggesting less proliferation and more differentiation of MS stem cells in DA-depleted striatum. Neither TH-positive neurons nor behavioral amelioration were detected following CTx stem (progenitor) cell transplantation in the striata. Data suggest that the DA-depleted striatum offers a suitable environment for MS stem (progenitor) cells to differentiate into mature DAergic neurons.

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