Showing papers by "Kunikazu Tanji published in 2003"
TL;DR: Findings indicate that, although not frequently, Bergmann glia of the cerebellum are also the targets of α- Synuclein pathology in α-synucleinopathies such as PD, DLBD and MSA.
Abstract: We carried out immunohistochemical examinations of the brains (cerebella) of patients who had suffered from Parkinson's disease (PD), diffuse Lewy body disease (DLBD) or multiple system atrophy (MSA), using antibodies specific for α-synuclein. α-Synuclein-positive doughnut-shaped structures were found occasionally in the cerebellar molecular layer in some of these patients. Double-labeling immunofluorescence and immunoelectron microscopy studies revealed that these α-synuclein-positive doughnut-shaped structures were located in the glial fibrillary acidic protein-positive radial processes of Bergmann glia, corresponding to the outer area of Lewy body-like inclusions, and consisted of granulo-filamentous structures. These findings indicate that, although not frequently, Bergmann glia of the cerebellum are also the targets of α-synuclein pathology in α-synucleinopathies such as PD, DLBD and MSA.
54 citations
TL;DR: It is shown that the expression ofMT-III is induced in cultured normal human astrocytes by hypoxia, and that overexpressed MT-III protects human embryonic kidney cells from hypoxIA, suggesting that MT- III can protect the brain from hypoxic damage.
30 citations
TL;DR: The early tau phosphorylation induced by IL-1&agr; might create a plastic environment for morphological changes in astrocytes.
Abstract: Tau phosphorylation is associated with neurite outgrowth and morphogenesis in neurons. Since inflammatory stimuli induce marked morphological changes in astrocytes, we examined the effect of interleukin 1alpha (IL-1alpha), an inflammatory cytokine, on the expression and phosphorylation of tau protein in cultured human astrocytes. Western blot analysis showed a rapid and transient increase (3-30 min) of tau phosphorylation at the AT8 epitope. The cells began to extend processes from 24 h after IL-1alpha stimulation. It is known that tau phosphorylation at the AT8 epitope reduces its ability to bind to, and stabilize, microtubules. The early tau phosphorylation induced by IL-1alpha might create a plastic environment for morphological changes in astrocytes.
18 citations
TL;DR: It is reported that synphilin‐1 is phosphorylated by glycogen synthase kinase‐3βin vitro, which may play an important role in the function of this protein in the brain.
Abstract: alpha-Synuclein is known to be a major component of Lewy bodies and glial cytoplasmic inclusions in the brains of patients with alpha-synucleinopathies. Synphilin-1, an alpha-synuclein-associated protein, is also present in these inclusions. However, little is known about the post-translational modifications of synphilin-1. In the present study, it is reported that synphilin-1 is phosphorylated by glycogen synthase kinase-3beta in vitro. It is well known that protein phosphorylation is involved in various physiological phenomena, including signal transduction and protein degradation. Therefore, phosphorylation of synphilin-1 may play an important role in the function of this protein in the brain.
14 citations
TL;DR: 15d-PGJ2 inhibits GM-CSF expression through a mechanism unrelated to PPAR-gamma, and induced the expression of interleukin-8, a potent proinflammatory chemokine, in HUVEC, suggesting that 15d- PGJ2 may regulate inflammatory reactions by controlling the balance of various cytokines.
10 citations
01 Jun 2003
TL;DR: It is concluded that vascular cells express α-synuclein, and it may play some role in the physiology of the vascular wall.
Abstract: α-Synuclein was originally identified as the precursor of non-amyloid β component of Alzheimer's disease amyloid (NAC). NAC is detected in cerebral amyloid angiopathy; and we studied whether cerebral vascular cells express α-synuclein. Immunohistochemical studies of normal human cerebral tissues revealed the expression of α-synuclein in vascular endothelial and smooth muscle cells. Also cultures of human umbilical vein endothelial cells and umbilical artery smooth muscle cells were found, by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis, to constitutively express α-synuclein mRNA. Western blot analysis disclosed the presence of α-synuclein protein in lysates of these cells. We conclude that vascular cells express α-synuclein, and it may play some role in the physiology of the vascular wall.
5 citations
01 Jun 2003
TL;DR: It is suggested that αS-immunoreactive glial inclusions may be a consequence of altered protein structure rather than de novo expression of αS and that a critical balance betweenαS and βS might be involved in inflammatory processes.
Abstract: α- and β-Synucleins (αS and βS) are concentrated in presynaptic nerve terminals. αS is now known to be a major component of Lewy bodies in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), as well as of oligodendroglial cytoplasmic inclusions in multiple system atrophy (MSA). Moreover, αS-positive inclusions in both astrocytic and oligodendroglial cells have also been detected in PD and DLB brains. However, these proteins have not been identified in glial cells in the normal human brain. We determined whether αS and βS might be expressed in glial cells. αS mRNA and protein were detected in normal human astrocytes and U251 human astrocytic glioma cells in vitro. Immunohistochemically, αS immunoreactivity was found in the cytoplasm of astrocytes and oligodendrocytes in vibratome sections of brain tissue taken from normal human subjects. βS immunoreactivity was also found in the astrocytes but not in the oligodendrocytes. Interleukin-1 increased the level of αS mRNA and protein in U251 cells, on the other hand, interleukin-1 decreased the level of βS mRNA and protein. These findings suggest that αS-immunoreactive glial inclusions may be a consequence of altered protein structure rather than de novo expression of αS and that a critical balance between αS and βS might be involved in inflammatory processes.
01 Jun 2003
TL;DR: Findings suggest that a significant amount of αS is also present in the neuronal and glial cytoplasm in the central and peripheral nervous systems.
Abstract: α-Synuclein (αS), a presynaptic nerve terminal protein, is now known to be a major component of neuronal and glial cytoplasmic inclusions in Lewy body (LB) disease and multiple system atrophy (MSA). However, αS has not been identified in either neuronal or glial cytoplasm in normal conditions. Recently, we demonstrated that αS was recognized by immunostaining in the cytoplasm of neurons, astrocytes and oligodendrocytes in vibratome sections, but not paraffin sections, from the normal human brain. Pretreatment with proteinase K and formic acid increased the intensity of αS immunoreactivity in these cells. The distribution of αS-immunoreactive neurons appears to be similar to that of intraneuronal inclusions in the brain of α-synuclein transgenic mice and the predilection sites for Lewy bodies. Moreover, αS was normally expressed in the cytoplasm of neurons and Schwann cells in the peripheral nervous system. These findings suggest that a significant amount of αS is also present in the neuronal and glial cytoplasm in the central and peripheral nervous systems. It is possible that specific upregulation and/or insufficient degradation of αS may contribute to inclusion body formation.
01 Jun 2003
TL;DR: PAF is known as a mediator of ischemic injury of the nervous tissues, and VEGF may be involved in part of the effect of PAF in brain hypoxia, which exerts a synergistic effect on the PAF-induced V EGF expression.
Abstract: Platelet-activating factor (PAF) has neuroregulatory activities and is implicated in ischemic injury of the brain. We found that PAF stimulates the expression of vascular endothelial growth factor (VEGF), a potent and specific mitogen for vascular endothelial cells, in normal human astrocytes. Reverse transcription-PCR (RT-PCR) demonstrated the enhancement, by PAF, of the VEGF mRNA expression in time- and concentration-dependent manners. The levels of VEGF protein in astrocyte-conditioned medium were determined by enzyme-linked immunosorbent assay, and 24-h stimulation with 10 nM PAF resulted in 1.3-fold increase in VEGF protein production. When the cells were subjected to hypoxia, the PAF-induced production of VEGF was enhanced by 6.7-fold as compared to the cells stimulated in a similar manner under normoxia. PAF stimulates VEGF expression in human astrocytes, and hypoxia exerts a synergistic effect on the PAF-induced VEGF expression. PAF is known as a mediator of ischemic injury of the nervous tissues, and VEGF may be involved in part of the effect of PAF in brain hypoxia.