PubMed Health⌕ Search

Biomedical subjects

Heii Arai

Publications and source records attributed to Heii Arai.

At least 19 recordsLinked to original sources
PubMed2006

Expression and localization of Parkinson's disease-associated leucine-rich repeat kinase 2 in the mouse brain.

Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) have been identified as the cause of familial Parkinson's disease (PD) at the PARK8 locus. To begin to understand the physiological role of LRRK2 and its involvement in PD, we have investigated the distribution of LRRK2 mRNA and protein in the adult mouse brain. In situ hybridization studies indicate sites of mRNA expression throughout the mouse brain, with highest levels of expression detected in forebrain regions, including the cerebral cortex and striatum, intermediate levels observed in the hippocampus and cerebellum, and low levels in the thalamus, hypothalamus and substantia nigra. Immunohistochemical studies demonstrate localization of LRRK2 protein to neurones in the cerebral cortex and striatum, and to a variety of interneuronal subtypes in these regions. Furthermore, expression of LRRK2 mRNA in the striatum of VMAT2-deficient mice is unaltered relative to wild-type littermate controls despite extensive dopamine depletion in this mouse model of parkinsonism. Collectively, our results demonstrate that LRRK2 is present in anatomical brain regions of direct relevance to the pathogenesis of PD, including the nigrostriatal dopaminergic pathway, in addition to other regions unrelated to PD pathology, and is likely to play an important role in the normal function of telencephalic forebrain neurones and other neuronal populations.

Animals↗
PubMed2006

Requirement of tryptophan hydroxylase during development for maturation of sensorimotor gating.

Deficits in sensorimotor gating, a function to focus on the most salient stimulus, could lead to a breakdown of cognitive integrity, and could reflect the "flooding" by sensory overload and cognitive fragmentation seen in schizophrenia. Sensorimotor gating emerges at infancy, and matures during childhood. The mechanisms that underlie its development are largely unclear. Here, we screened the mouse genome, and found that tryptophan hydroxylase (TPH) is implicated in the maturation of sensorimotor gating. TPH, an enzyme involved in the biosynthesis of serotonin, proved to be required only during the weaning period for maturation of sensorimotor gating, but was dispensable for its emergence. Proper serotonin levels during development underlie the mature functional architecture for sensorimotor gating via appropriate actin polymerization. Thus, maintaining proper serotonin levels during childhood may be important for mature sensorimotor gating in adulthood.

Acoustic Stimulation↗
PubMed2006

Immunohistochemical investigation of neurofibrillary tangles and their tau isoforms in brains of limbic neurofibrillary tangle dementia.

Limbic neurofibrillary tangle dementia (LNTD) is a subset of senile dementia characterized by numerous neurofibrillary tangles (NFT) in the hippocampal area, although there is an absence or scarcity of amyloid deposits (AM) throughout the brain. In the present study, we immunohistochemically investigated regional numbers and tau isoforms of NFT in the hippocampal area of nine LNTD patients with anti-three-repeat (3R) tau-specific and anti-four-repeat (4R) tau-specific antibodies, differentiating NFT into three developmental stages of pretangles (PT), NFT and ghost tangles (GT). Consequently, most PT were 4R tau-positive, most GT were 3R tau-positive, and NFT were 3R tau-, 4R tau- or double-positive, suggesting that composition of tau isoforms may shift from a 4R tau-predominant pattern to a 3R tau-predominant pattern during the development of NFT. In addition, a large number of NFT showing different developmental stages and different rates of 3R tau- and 4R tau-positive neurons according to the region were found in the hippocampal area, suggesting that regions undergoing earlier NFT formation may show higher ratio of 3R tau-positive neurons to 4R tau-positive neurons, and that NFT formation may begin in the entorhinal and transentorhinal cortices, subsequently progress to the subiculum and CA1, and further to the CA2, amygdala and CA3-4, although progression to the neocortex is limited. Furthermore, 4R tau-positive astrocytes and grains were found in several patients, suggesting that LNTD is a form of tauopathy.

Aged, 80 and over↗
PubMed2006

Relative paucity of tau accumulation in the small areas with abundant Abeta42-positive capillary amyloid angiopathy within a given cortical region in the brain of patients with Alzheimer pathology.

Cerebral amyloid angiopathy (CAA) is a manifestation of amyloid beta-protein (Abeta) accumulation in the elderly as well as in patients with Alzheimer's disease (AD). Two types of CAA have been noted, based on the type of vasculature in which Abeta is deposited: cerebral capillary amyloid angiopathy (capCAA) and non-capCAA. Non-capCAA is a common form of CAA that consists of Abeta deposited in arteries and arterioles. Recent information on Abeta metabolism in the brain suggests that non-capCAA is associated with Abeta secretion into the cerebrospinal fluid via the perivascular space, whereas capCAA is associated with Abeta removal to blood plasma via the capillary endothelium. Abeta40, a major and relatively soluble Abeta isoform, is deposited predominantly in non-capCAA, and Abeta42, which is insoluble and associated more closely than Abeta40 with AD, is deposited predominantly in capCAA. Studying small areas of microscopic size within a given cortical region, we found an inverse association of capCAA and senile plaques. We also found a relative paucity of tau pathology in the small areas with abundant capCAA compared with the small areas with abundant senile plaques within a cortical region with the same cytoarchitecture. We suppose that both capCAA and senile plaques indicate high Abeta42 in the neuropil but that only Abeta42 in the form of insoluble deposits in senile plaques promotes tau abnormality.

Aged↗
PubMed2006

Déjà vu experiences in patients with schizophrenia.

To investigate whether déjà vu experiences are psychopathologic phenomena, we studied the frequency and characteristics of déjà vu experiences in patients with schizophrenia. One hundred thirteen patients with schizophrenia and 386 nonclinical control subjects were evaluated with the Inventory of Déjà vu Experiences Assessment. The frequency and features of déjà vu experiences were compared between the 2 groups. The patients with schizophrenia had déjà vu experiences less frequently (53.1%) than did the nonclinical subjects (76.2%). The frequency of déjà vu experiences did not correlate significantly with age at evaluation or education level among the patients with schizophrenia. Most characteristics of déjà vu experiences of the patients were comparable with those of the control subjects. However, the experiences of the patients tended to be longer and more monotonous. The patients often felt alert, oppressed, and disturbed by the experiences. They appeared to have the experiences under unpleasant mental or physical states. Their déjà vu experiences are not primarily different in nature from those of the nonclinical subjects. The decreased frequency of the experiences in the patients may suggest déjà vu experiences as nonpathologic phenomena.

Adult↗
PubMed2006

Investigation of Lewy pathology in the visual pathway of brains of dementia with Lewy bodies.

We examined 19 autopsied cases of dementia with Lewy bodies (DLB) using pathological and alpha-synuclein-immunohistochemical methods, and investigated Lewy pathology in the primary visual pathway (lateral geniculate body and Brodmann's area 17), secondary visual pathway (pulvinar, Brodmann's areas 18 and 19, and inferior temporal cortex), amygdala and substantia nigra, to clarify the relationship between visual misidentification and Lewy pathology in the visual pathway. Consequently, the secondary visual pathway revealed significantly severer Lewy pathology than the primary visual pathway, suggesting that the degeneration of the secondary visual pathway induces dysfunction in the recognition of objects shape and color. In addition, the amygdala revealed significantly severer Lewy pathology and neuronal loss than the primary and secondary visual pathways, suggesting that the degeneration of the amygdala, which receives the afferent connections from the substantia nigra, fails to modulate the visual processing according to cognition and emotion. These findings suggest that Lewy pathologies in the secondary visual pathway and amygdala may cause the dysfunction of the visuo-amygdaloid pathway and participate in visual misidentification in DLB patients. In addition, we compared Lewy pathology between cases with and without visual hallucinations, and showed no significant differences between the two groups.

Aged↗
PubMed2006

No genetic association between postsynaptic density-95 gene polymorphisms and schizophrenia.

Disturbed glutamatergic neurotransmission, especially disturbed N-methyl-D-aspartate (NMDA) receptor function, has been hypothesized to be involved in the pathophysiology of schizophrenia. It may also involve abnormalities in the intracellular signaling machineries that are linked to the NMDA receptor. Postsynaptic density-95 is known to bind NMDA receptor subunits and is involved in intracellular signal transduction and synaptic plasticity. Recently, we reported that gene expression of postsynaptic density-95 was altered in schizophrenic brains compared to controls. Therefore, in this study, we examined six polymorphisms in and around the postsynaptic density-95 gene in 259 schizophrenic cases and 188 healthy controls using TaqMan technology. The results suggested that these six polymorphisms did not affect risk for schizophrenia.

Adult↗
PubMed2006

Case reports and literature review: the association between reactivation of human herpes virus-6 and peripheral white blood cell count in patients with carbamazepine-induced hypersensitivity syndrome.

Eruptions induced by anticonvulsants can often be experienced clinically, and the clinical diagnosis of "drug induced hypersensitivity syndrome (HS)" was proposed to characterize these drug eruptions. Reactivation of human herpes virus-6 seems to be an integral component of HS. Previously, we experienced two cases of carbamazepine (an anticonvulsant) induced HS and both cases did not show a reactivation of human herpes virus-6 infection (no elevation of anti-human herpes virus-6 IgG titres). The features of these two cases were compared with other reported cases that presented HS with the reactivation of human herpes virus-6. In the early phase of HS, a change in peripheral white blood cell count seems to be important and could be used as an indicator to predict whether late phase HS with reactivation of human herpes virus-6 will occur, since the increase in white blood cell count is seen before the increase in anti-human herpes virus-6 titres. Reactivation of human herpes virus-6 may cause severe clinical symptoms such as encephalitis. When an increase in white blood cells are observed in HS cases at onset, immediate discontinuation of cause drug and intensive care are necessary to avoid the more severe symptoms of HS.

Adult↗
PubMed2006

Electroconvulsive therapy improves severe pain associated with fibromyalgia.

The pathophysiology of fibromyalgia remains unknown. Several reports have recently suggested the novel concept that fibromyalgia is due to the central nervous system becoming hyper-responsive to a peripheral stimulus. The effect of electroconvulsive therapy (ECT) as pain remedication in cases of fibromyalgia without major depressive disorder was studied in a prospective trial lasting three months. All of the patients taking part in the study fulfilled the American College of Rheumatology diagnostic criteria for fibromyalgia. Technetium-99m ethyl cysteinate dimer single photon emission computed tomography was used to assess regional cerebral blood flow (rCBF) before and after a course of ECT. Pain assessment in the patients was undertaken by use of the visual analog scale (VAS) and by evaluation of tender points (TPs). Beck's depression inventory (BDI) was further used to assess depressive mood change in the patients. Our study clearly demonstrated that pain was significantly less severe after ECT, as indicated by the VAS scale for pain and the evaluation of TPs. A further notable observation was that thalamic blood flow was also improved. We conclude that a course of ECT produced notable improvements in both intractable severe pain associated with fibromyalgia and also in terms of thalamic blood flow.

Adult↗
PubMed2006

No genetic association between the myeloperoxidase gene -463 polymorphism and estrogen receptor-alpha gene polymorphisms and Japanese sporadic Alzheimer's disease.

Myeloperoxidase (MPO) presence has been demonstrated in microglia associated with senile plaques and contributes to Alzheimer's disease (AD) pathology through oxidation-induced damage. MPO activity is normally higher in women than in men. Additionally, a functional biallelic (G/A) polymorphism in the promoter region (-463) of the MPO gene has been associated with a gender-specific risk factor for AD, but reports of this association have been inconsistent. Furthermore, estrogen is known to enhance MPO activity in myeloid cells and increases the amount of MPO in plasma. Recently, estrogen replacement therapy has been reported to reduce the risk of developing AD and to help maintain cognitive function in patients with AD. In the current study, we analyzed the MPO -463 polymorphism and two estrogen receptor-alpha polymorphisms in 205 Japanese sporadic AD patients and 92 controls. The results suggest that there is no significant difference in the genotypic frequencies and allelic frequencies of the MPO -463 polymorphism and the estrogen receptor-alpha polymorphisms between the Japanese sporadic AD group and the control group.

Aged↗
PubMed2006

A quantitative near-infrared spectroscopy study: a decrease in cerebral hemoglobin oxygenation in Alzheimer's disease and mild cognitive impairment.

A newly developed quantitative near-infrared spectroscopy (NIRS) system was used to measure changes in cortical hemoglobin oxygenation during the Verbal Fluency Task in 32 healthy controls, 15 subjects with mild cognitive impairment (MCI), and 15 patients with Alzheimer's disease (AD). The amplitude of changes in the waveform, which was quantitatively calculated by a signal processing method, was significantly lower in the frontal, and the bilateral parietal areas in the AD group, whereas that in the MCI group was significantly lower only in the right parietal area. The NIRS system may be a potential tool for the primary screening of AD.

Alzheimer Disease↗
PubMed2006

Effects of repeated phencyclidine administration on adult hippocampal neurogenesis in the rat.

Dysfunctional maturation of neural networks, particularly hippocampus-prefrontal networks, may be of particular interest in determining the pathophysiology of schizophrenia. Phencyclidine (PCP)-induced symptoms in humans appear to offer a more complete model of schizophrenia than do amphetamine-induced symptoms. This study investigated the effects of intermittent i.p. injections of PCP (7.5 mg/kg) on cell proliferation and survival of granule cells in the dentate gyrus of the rat brain using quantitative immunohistochemical techniques for 5-bromo-2'-deoxyuridine (BrdU)-positive cells. After repeated PCP injection for 14 days, mean scores for stereotyped behavior increased with the number of injections, while scores for ataxia and backpedaling as serotonergic behaviors gradually decreased. The number of BrdU-positive cells decreased by 23% in the subgranular zone of the dentate gyrus by 24 h after repeated injections. However, decreased levels of BrdU-positive cells returned to control levels within 1 week. Differentiation of newly formed cells was not influenced. Repeated PCP administration after BrdU injection did not exert any effects on survival of newly generated cells. These findings suggest that transient disturbances of cell proliferation in the dentate gyrus occur under PCP-related behavioral abnormalities. Whether disturbed cell proliferation would thus be closely implicated in the development of behavioral sensitization induced by PCP administration is unclear, but this would possibly result from adaptation to new pharmacological conditions under behavioral sensitization or stressful conditions of PCP-related abnormal behaviors. Further studies are required to elucidate the biological significance of hippocampal neurogenesis in the mechanisms underlying the development of cognitive dysfunctions and the psychosis of schizophrenia.

Animals↗
PubMed2006

Genetic association between USF 1 and USF 2 gene polymorphisms and Japanese Alzheimer's disease.

To investigate the effect of single nucleotide polymorphisms (SNPs) of the upstream stimulatory factor (USF) 1 and 2 genes on the onset of Alzheimer's disease (AD), a case-control study was performed. The SNPs were genotyped by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 236 AD patients and 120 age-matched controls of Japanese descent. We observed no significant association between the three SNPs of the USF 1 gene and AD in our Japanese participants. In addition, the SNPs studied did not affect plasma cholesterol levels in our AD cases. For the USF 2 gene, the two SNPs did not show significant association with onset of AD. Our study suggests that the three SNPs of the USF 1 gene and two SNPs of the USF 2 gene presented here are not associated with onset of AD.

Adult↗
PubMed2006

Self-administered electroconvulsive treatment with a homemade device.

Two patients with personality disorder and depression attempted to self-administer electroconvulsive therapy with a homemade device. The patients showed no proper psychopathological improvement after these attempts. Both of the patients' temples were seriously burned, and one of them required skin grafting. Both patients rejected to have reasonable psychosocial support, and followed a cult mental health manual in attempting to self-administer electroconvulsive therapy. To our knowledge, this is only the second report of its kind. The intractable psychopathology, poor interpersonal skills, and misleading information seemed to lead to the self-harm behaviors of our 2 patients.

Adult↗
PubMed2006

Genetic association between Notch4 polymorphisms and Japanese schizophrenics.

The objective of this study was to investigate whether three single nucleotide polymorphisms of the Notch4 gene are associated with the onset of schizophrenia. To confirm the linkage disequilibrium among these three single nucleotide polymorphisms of the gene, the three single nucleotide polymorphisms were genotyped by a polymerase chain reaction-restriction-fragment length polymorphism method for all samples. The genotypic frequencies of each single nucleotide polymorphism in the schizophrenic were compared with respective controls using a chi method. To check linkage disequilibrium, the haplotype frequency program was utilized. No statistical association between the two single nucleotide polymorphisms of the Notch4 gene and schizophrenia was observed in our Japanese samples. Although one nonsynonymous single nucleotide polymorphism did show a weakly significant P-value, its allelic frequencies are not positive. Two of the single nucleotide polymorphisms showed strong linkage disequilibrium in our Japanese samples. The single nucleotide polymorphism between the other two single nucleotide polymorphisms showed a weaker linkage disequilibrium with the others. Our study suggests that the three single nucleotide polymorphisms are not associated with the onset of schizophrenia. The linkage disequilibrium of this locus indicates that there is genetic heterogeneity in the Notch4 gene. Linkage disequilibrium may differ among ethnic groups, and so a larger study should be performed in this region.

5' Untranslated Regions↗
PubMed2005

Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p.

The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study--which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent--indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.

Chromosomes, Human, Pair 1↗