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Heii Arai

Publications and source records attributed to Heii Arai.

At least 37 records · Page 2Linked to original sources
PubMed2005

No genetic association between ATP binding cassette proteins and Japanese sporadic Alzheimer's disease.

The identification of the epsilon4 variant of apolipoprotein E as a genetic risk factor for late-onset Alzheimer's disease (AD) suggests that cholesterol may play a direct role in the pathogenesis of the disease. Recent studies have suggested that the ATP-binding cassette (ABC) protein G5 (ABCG5) may be involved in the regulation of intestinal cholesterol absorption. Furthermore, genetic variation of this locus may affect blood cholesterol concentrations. We therefore studied whether the ABCG5 C1950G (Gln640Glu) polymorphism affects the risk of AD. In addition, there was no difference in mean baseline cholesterol concentrations between individuals with the C/C genotype and carriers of the G allele. Recent studies have shown that genetic regions including the ABCA12 gene might also be associated with the risk of AD. The ABCA12 gene, located <1 Mb from the peak marker on chromosome 2q34, is also a member of the ABC transporter superfamily. In the current study, two common polymorphisms of the ABCA12 gene, rs952718 (T/G) and rs956133 (A/G), were analyzed in our subjects. These polymorphisms showed no association with the risk of AD. Furthermore, we observed weak linkage disequilibrium between these two single nucleotide polymorphisms. These results indicate that the common polymorphisms of the ABCG5 and ABCA12 genes investigated here are not associated with AD.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2005

The nigro-striatal and nigro-amygdaloid pathways undergo different degeneration processes in brains of dementia with Lewy bodies.

We immunohistochemically investigated the degeneration processes of the nigro-striatal and nigro-amygdaloid pathways and the relationship between the loss of dopaminergic neurons and Lewy bodies (LB) formation in the substantia nigra using 15 autopsied cases of dementia with Lewy bodies (DLB). The number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra and TH-positive axonal terminals in the putamen decreased with a specific pattern. The substantia nigra possessed alpha-synuclein-positive LB-bearing neurons that were almost evenly distributed, while the putamen exhibited diffuse or granular alpha-synuclein-immunostaining. Most of the granular stains were positive for anti-phosphorylated alpha-synuclein antibody, whereas the diffuse stains were negative. These findings suggest that the axonal terminals in the putamen undergo abnormal alpha-synuclein accumulation, but may not always originate from LB-bearing neurons in the substantia nigra. The central amygdaloid nucleus contained anti-alpha-synuclein- and -phosphorylated alpha-synuclein-positive dystrophic axonal terminals, the degree of which was greater for cases with granular staining in the putamen, and which was proportional to the number of alpha-synuclein-positive neurons in the substantia nigra. Thus, the axonal terminals in the central amygdaloid nucleus may have originated from LB-bearing neurons in the substantia nigra. The results of the present study indicate that the nigro-striatal and nigro-amygdaloid pathways undergo different degeneration processes in DLB, and suggest that the degeneration of the nigro-amygdaloid pathway more strongly reflects LB formation in dopaminergic neurons of the substantia nigra than that of the nigro-striatal pathway. In addition, they indicate that there is no direct relationship between the loss of dopaminergic neurons and LB formation in the substantia nigra.

Aged↗
PubMed2005

Decreased cell proliferation in the dentate gyrus of rats after repeated administration of cocaine.

Cell proliferation in the dentate gyrus of hippocampus was assessed using in vivo labeling with 5-bromo-2'-deoxyuridine (BrdU) in adult rats that were administered cocaine (20 mg/kg) for 14 consecutive days. Rats showed increased stereotypy at a challenge dose of cocaine after 1 week of withdrawal, suggesting the acquisition of behavioral sensitization. Twenty-four hours after final injection of repetitive cocaine administration, a 26% decrease in BrdU-positive cells was observed, compared with control rats. However, this returned to control level within 1 week. No differences were observed in rats that received a single injection of cocaine. Differentiation of newly formed cells was not influenced. These data imply that the regulation of hippocampal cell proliferation by cocaine may be involved in the development of certain symptoms of addiction, such as cognitive impairment and acquisition of behavioral sensitization.

Animals↗
PubMed2005

Transdermal nicotine administration enhances automatic auditory processing reflected by mismatch negativity.

Mismatch negativity (MMN) is a component of event-related potentials (ERPs) with a wide-ranging applicability to the investigation of neuronal substrates of information processing in normal and psychopathological states. Nicotine has been shown to be implicated in the pathophysiology of psychiatric disorders as schizophrenia or Alzheimer's disease, and has also been proposed as a self-administered drug in schizophrenia. The goal of the present study is to elucidate the effect of nicotine on the auditory automatic processing reflected by MMN. Nicotine was administered transdermally under controlled dosage. Ten healthy volunteers attended the laboratory for one baseline session and two test sessions. The test sessions involved administration of a placebo patch and a nicotine skin patch, which were counter-balanced. The ERPs were recorded passively during an auditory oddball paradigm. Nicotine administration shortened the MMN latencies, and these effects were independent of the earlier ERP components, N100 and P200. In conclusion, nicotine enhances preattentive and automatic processing such as MMN system and these effects appear to be quite specific and independent of earlier cognitive stages than preattentive mismatch processing. The shortened MMN latency may be interpreted as a reduction of the amount of time required to complete a neuronal mismatch process through the ascending auditory pathway.

Acoustic Stimulation↗
PubMed2005

Hypothesis: minimal changes in neural transmission in schizophrenia: decreased glutamatergic and GABAergic functions in the prefrontal cortex.

As the pathophysiology, decreased glutamatergic neurotransmission in the postmortem prefrontal cortex of schizophrenics has been suggested to underlie the condition. But consistent reproducible results have not been seen with the molecular biological studies focused on examining glutamatergic parameters in schizophrenic brains. We noticed the lack of reproducibility of these studies and hypothesized that this was caused by "minimal (functional) changes" of schizophrenic pathophysiology that cannot be detected as a robust result by investigating only one marker (i.e., receptor). The authors then investigated glutamate levels, as well as mRNA expression of glutamate receptors and transporters simultaneously for the same schizophrenic and control brain samples, in order to detect the "minimal changes" of glutamatergic neurotransmission in schizophrenic synaptic clefts. The results showed a tendency of increased mGluRs and decreased EAAT2 mRNA in all Brodmann areas examined, but no significant difference was observed between schizophrenics and controls. To make these small changes of glutamatergic neurotransmission on the synaptic clefts more apparent, the "receptors/transporters ratio" (mGluRs/EAAT2 ratio) was calculated for each case and the results showed that the mGluRs/EAAT2 ratio was significantly increased in schizophrenics compared to controls. Glutamate levels, measured by HPLC, showed a decrease in the schizophrenics, but failed to reach statistical significance. The same phenomenon was recognized in our GABAergic study of schizophrenic brain. To interpret these results as a monism, the increase in mGluRs and the decrease of EAAT2 mRNA compensate for the decrease in glutamate transmission in the schizophrenic synaptic clefts. But these changes are small and failed to be statistically significant. The "receptors/transporters ratio" for each case magnified these changes, such that they became statistically significant.

Animals↗
PubMed2005

Non-uniformity in the regional pattern of Lewy pathology in brains of dementia with Lewy bodies.

We examined the regional pattern of Lewy pathology in brains of dementia with Lewy bodies (DLB) to clarify whether Lewy pathology uniformly progresses or not. Thirty-five autopsied DLB cases were examined using alpha-synuclein-immunohistochemistry, and the regional degree of Lewy pathology in the brainstem, diencephalon and cerebral cortex was quantitatively evaluated. Consequently, we found that the regional pattern of Lewy pathology differed according to the pathological subtype, and was divided into three types: type 1 showed a brainstem-predominant pattern, type 2 was almost equal for the brainstem and cerebral cortex, and type 3 showed a cerebral cortex-predominant pattern. The limbic type/pure and common forms were mainly composed of type 1, whereas the neocortical type/common and Alzheimer's disease (AD) forms were mainly composed of type 3. These findings suggest the possibility that Lewy pathology of the limbic type/pure and common forms mainly progresses from the brainstem to the cerebrum, whereas that of the neocortical type/common and AD forms mainly progresses from the cerebrum to the brainstem. Cases with type 1 Lewy pathology mainly developed parkinsonism, whereas those with type 3 Lewy pathology mainly developed dementia. This corresponded to most of the limbic type/ pure and common forms which developed parkinsonism, whereas most of the neocortical type/common and AD forms developed dementia. Type 1 cases may thus be clinically diagnosed as having Parkinson's disease (PD) with dementia. These findings suggest that PD has clinico-pathological continuity with DLB, and that the regional pattern of Lewy pathology is not uniform.

Aged↗
PubMed2005

[Autopsy case of Lewy body dementia associated with abundant argyrophilic grains].

We report an autopsy case showing neuropathologically abundant Lewy bodies and argyrophilic grains. A Japanese woman without hereditary burden developed parkinsonian gait at the age of 74, following by insomnia, memory disturbance, delirium, resting tremor, rigidity, and retropulsion. About 8 months later, a visual hallucination, concerning small worms, children, and so on, became obvious. About 16 months later, malignant lymphoma was detected. About 17 months later, she died of pneumonia. The total duration of illness was approximately one year and five months. The weight of the brain was 1153 g before fixation. Depigmentation of the substantia nigra and locusceruleus was prominent. Many argyrophilic grains were seen in the temporal lobe (T3, T4), amygdala, and hippocampal CA1. Some ballooned neurons were found in the amygdala. Many Lewy bodies were encountered in the transentorhinal region and cingulated gyrus. A few Lewy bodies were seen in the temporal, frontal, and parietal lobes. In this case, neuropathological examination is compatible for dementia of Lewy bodies and argyrophilic grain dementia, and clinical course is consistent with dementia of Lewy bodies. This report may contribute to the elucidation of the clinicopathological hallmarks of argyrophilic grain dementia and dementia with Lewy bodies.

Aged↗
PubMed2004

Effects of single and repeated phencyclidine administration on [3H]flunitrazepam binding in rat brain.

Repeated administration of phencyclidine (PCP) induces behavioral sensitization to dopaminergic neural transmission. This phenomenon has been implicated in the pathophysiology of schizophrenia. Recently, GABAergic agonists have been shown to reduce behavioral activity induced by enhanced dopaminergic neural transmission, which is mediated by the GABA(A)/benzodiazepine (BZD) receptor complex. Thus, to investigate the role of BZD receptors during induction and expression of behavioral sensitization in PCP-sensitized animals, the effects of both single and repeated PCP administration on BZD receptors in rat brain were examined using in vitro quantitative autoradiography. Repeated PCP administration failed to significantly alter levels of [3H]flunitrazepam (FNZ) binding in any of the regions examined. However, significant increases in levels of [3H]FNZ binding were found in the nucleus accumbens and ventral pallidum 1 h after single administration of PCP. These results suggest that BZD binding sites may not play important roles in the development of PCP-induced sensitization at several sites of GABA(A)/BZD receptor complex, while changes in GABA function in the nucleus accumbens differ from other areas following single administration of N-methyl-D-aspartate (NMDA) antagonist.

Animals↗
PubMed2004

Genetic association between matrix metalloproteinase MMP-9 and MMP-3 polymorphisms and Japanese sporadic Alzheimer's disease.

Recent studies suggested that matrix metalloproteinases (MMPs) might play an important role in the pathophysiology of Alzheimer's disease (AD). MMP-9 and MMP-3 are reported to degrade amyloid beta and have several functional polymorphisms associated with other common diseases. Four common polymorphisms in each of MMP-9 and MMP-3 were examined in AD cases and normal control individuals. Common polymorphisms of MMP-9, rs3918248, rs2664538, rs2250889 and rs2274756 showed no association with risk for AD. We observed strong linkage disequilibrium (LD) between rs2664538 and rs2250889 in our Japanese samples. The polymorphisms of MMP-3; 5A/6A insertion polymorphism in the promoter, rs3025079, rs520540 and rs679620 also did not influence risk for AD. LD of the 5A/6A polymorphism with rs679620 was relatively strong. These results suggest that the common polymorphisms of MMP-9 and MMP-3 investigated here are not associated with AD.

Adult↗
PubMed2004

No genetic association between Fyn kinase gene polymorphisms (-93A/G, IVS10+37T/C and Ex12+894T/G) and Japanese sporadic Alzheimer's disease.

Several groups have reported that abnormal phosphorylation of tau by Fyn, a protein-tyrosine kinase, may play a role in the neuropathogenesis of Alzheimer's disease (AD). In the present study, three common Japanese polymorphisms of the Fyn gene (-93A/G in the 5'-flanking region, IVS10+37T/C in intron 10 and Ex12+894T/G in the 3'-untranslated region) were studied in 127 healthy controls and 182 sporadic AD cases using a polymerase chain reaction restriction fragment length polymorphism method. A comparison of the allelic and genotypic frequencies of these polymorphisms between controls and sporadic AD cases failed to show any significant difference. These results suggest that the Fyn polymorphisms (-93A/G, IVS10+37T/C and Ex12+894T/G) investigated here have no genetic association with sporadic AD.

Adult↗
PubMed2004

Expression of nNOS and soluble guanylate cyclase in schizophrenic brain.

Recent evidence suggests that nitric oxide (NO) systems are affected in the pathophysiology of schizophrenia. We quantified levels of neuronal NO synthase (nNOS) and soluble guanylate cyclase (sGC) subunit mRNAs in the prefrontal cortex of post-mortem brains from individuals with schizophrenia and controls using real-time quantitative PCR, to determine whether levels of nNOS and sGC subunits are altered in 'schizophrenic' brains. Neuronal NOS expression in the prefrontal cortex was significantly higher in individuals with schizophrenia, whereas no significant changes were found in sGC subunit mRNAs in people with schizophrenia or in controls. Abnormalities of nNOS expression in the brain might contribute to the development of schizophrenia.

Adult↗
PubMed2004

A simple method for the detection of abnormal brain regions in Alzheimer's disease patients using [11C]MP4A: comparison with [123I]IMP SPECT.

We have developed a radiolabeled lipophilic acetylcholine analogue, N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) to measure brain acetylcholinesterase (AChE) activity by positron emission tomography (PET) in vivo. Aiming to develop a new SPECT tracer similar to MP4A, we first proposed a simple method for diagnosing Alzheimer's disease (AD) using [11C]MP4A PET. We performed [11C]MP4A PET and N-isopropyl [123I]iodoamphetamine ([123I]IMP) SPECT in 13 patients with AD and in 17 normal controls (NC). We calculated the ratio of radioactivity of the cortical region of interest (ROI) to that of the cerebellum measured with [11C]MP4A PET (MP4A ratio) and the ratio of regional cerebral blood flow (rCBF) to that of the cerebellum measured with [123I]IMP SPECT (IMP ratio). Eleven cortical ROIs were placed in the frontal, sensorimotor, temporal, parietal, and occipital cortices in both hemispheres and in the posterior cingulate cortex, and z-score was calculated in each ROI in patients with AD compared with NC. When the z-score was 2 or more in a ROI, it was defined as a positive ROI. When a patient had 3 or more positive ROIs, the patient was diagnosed as having AD. The reduction in the MP4A ratio was greater than that in the IMP ratio in all cortical ROIs except for in the right parietal cortex and cingulate cortex in patients with AD. MP4A ratio method showed 92% sensitivity and the IMP ratio method 69% sensitivity for the diagnosis of AD. These results encourage us to develop a new SPECT tracer similar to MP4A for the diagnosis of AD.

Acetates↗
PubMed2004

Irreversible subcortical dementia following high altitude illness.

In this report, we present the cases of two 63-year-old women who developed high altitude cerebral edema complicated by the occurrence of permanent neuropsychiatric sequelae. They shared a similar clinical course, in that both developed disturbance of consciousness shortly after their arrival at Cuzco, Peru (3500 m), and both developed persistent neuropsychiatric symptoms after resolution of the acute illness. Interestingly, in case 2 there was a 1-month lucid interval between remission of high altitude illness and occurrence of the irreversible neuropsychiatric sequelae. Brain computerized tomography in case 1 and brain magnetic resonance imaging in case 2 disclosed lesions in the globus pallidus bilaterally, suggesting that the neuropsychiatric symptoms in these patients were manifestations of subcortical dementia. The development of high altitude illness was considered to be attributable to mild restrictive lung impairment in case 1 and to a deficient ventilatory response to hypoxia in case 2. It must therefore be borne in mind that irreversible subcortical dementia may be associated with high altitude cerebral edema.

Acute Disease↗
PubMed2004

No genetic association between tumour necrosis factor receptor II 196R polymorphism and Japanese sporadic Alzheimer's disease.

Recent studies have reported that acute effects of tumour necrosis factor (TNF), a pro-inflammatory cytokine, are limited by binding to a soluble receptor, TNF receptor II, and the G allele at position 196 in exon 6 of the TNF receptor II gene (TNFRII 196R) has been associated with auto-immune diseases. Since complex interactions among cytokines have been suggested around senile plaques in Alzheimer's disease, TNF might be associated with ageing and the pathophysiology of Alzheimer's disease. We examined the TNFRII 196R polymorphism in 243 Japanese sporadic Alzheimer's disease cases and 106 control cases using a polymerase chain reaction-restriction fragment length polymorphism method. Allelic frequencies with TNFRII 196R T/G polymorphism were 28.3% and 27.4% in the control and Alzheimer's disease groups, respectively. The results showed no genetic association between TNFRII 196R polymorphism and Alzheimer's disease. The TNFRII 196R G allele does not appear to be associated with Alzheimer's disease susceptibility in a Japanese population.

Adult↗
PubMed2004

[An autopsy case of "progressive supranuclear palsy" without psychiatric or neurological signs].

We report an autopsy case of a Japanese man with "progressive supranuclear palsy (PSP)" who showed neither neurological nor psychiatric signs. Although he died by heart failure at the age of 84 years, he had neither neurological nor psychiatric signs throughout the clinical course. Neuropathological examination revealed neuronal loss of the substantia nigra and pallidum. Neurofibrillary tangles were observed in the caudate nucleus, subthalamic nucleus, pallidum, putamen, substantia nigra, locus ceruleus, pontine nucleus, inferior olivary nucleus, and dentate nucleus, compatible with the NINDS pathological diagnosis of PSP reported in 1994. Staining by Gallyas-Braak methods disclosed tuft-shaped astrocytes in the caudate nucleus, putamen, and thalamus. To our knowledge, this is the first report of "PSP" without psychiatric or neurological signs.

Aged↗
PubMed2004

[An autopsy case of senile dementia with pathological features of Parkinson's disease].

We report an autopsy case of Parkinson's disease mimicking senile dementia of the Alzheimer type. A Japanese man developed memory disturbance and visual hallucination at age 70. Although he died from pneumonia at age of 74, he had no neurological signs throughout the clinical course. The weight of his brain was 1,420 g. Macroscopic examination of the brain revealed prominent depigmentation of the substantia nigra and locus ceruleus. Histological examination disclosed neuronal loss with astrocytosis and the appearance of the Lewy bodies in the nucleus basalis of Meynert, substantia nigra, locus ceruleus, and dorsal vagal nucleus. There were widespread senile plaques in the brain, including the precentral gyrus, which was compatible with Braak stage C. A small number of neurofibrillary changes were present in the limbic areas, consistent with Braak stage III. This case is consistent with brain stem dominance with the pathological diagnosis of the Consortium on Dementia with Lewy Bodies International Workshop. That is, it is compatible with Parkinson's disease. We postulate that the clinical features of Parkinson's disease are more widespread than previously considered.

Aged↗
PubMed2003

No genetic association between polymorphisms in the Fyn kinase gene and age of schizophrenic onset.

Since the mRNA level of Fyn, a neurodevelopmental molecule, expression had been reported to be increased in postmortem schizophrenic prefrontal cortex and showed a strong correlation with age of disease onset, we investigated whether the three polymorphisms of the Fyn gene on genomic DNA (-93A/G, IVS10+37T/C and Ex12+894T/G) also had an effect on clinical onset in 139 unrelated schizophrenics. A comparison of the age of onset among the groups classified by polymorphisms showed no significant difference. Moreover, all allelic combinations also failed to show significant differences in age of onset among the groups. The present study reports that there is no indication that the three polymorphisms in the Fyn gene are associated with the age of schizophrenic onset.

Adolescent↗