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Koichi Wakabayashi

Publications and source records attributed to Koichi Wakabayashi.

At least 19 recordsLinked to original sources
PubMed2006

Degeneration of cardiac sympathetic nerve can occur in multiple system atrophy.

Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [(123)I] MIBG myocardial scintigraphy, a sensitive biological marker for Parkinson's disease (PD), is related to cardiac sympathetic denervation in patients with PD. A slight decrease in cardiac uptake of MIBG has also been reported in some patients with multiple system atrophy (MSA). However, the pathophysiological mechanism accounting for the slight decrease in MIBG uptake in MSA remains to be elucidated. For confirmation, we examined cardiac tissue and sympathetic ganglia from patients with MSA. We immunohistochemically examined each specimen of 15 patients with MSA together with 10 control subjects using antibodies against tyrosine hydroxylase (TH) and neurofilament (NF). The number of TH-immunoreactive nerve fibers in the epicardium was preserved in 8 of 15 patients with MSA as well as in 10 control subjects. The number of TH-immunoreactive, but not of NF-immunoreactive nerve fibers in the epicardium was mildly or moderately decreased in six patients with MSA, of whom four showed a decrease of TH immunoreactivity in the neuronal somata in the sympathetic ganglia. Moreover, TH- and NF-immunoreactive nerve fibers almost entirely disappeared in the heart of one patient with MSA, in whom Lewy body pathology was present in the sympathetic ganglia. These findings suggest that mild degeneration of the cardiac sympathetic nerve can occur in MSA which is closely related to the pathological change of neurons in the sympathetic ganglia, accounting for the slight decrease in cardiac uptake of MIBG. Moreover, concurrent Lewy body pathology in the sympathetic ganglia might accelerate cardiac sympathetic denervation even in MSA.

Adrenergic Fibers↗
PubMed2006

Effects of interleukin-1beta on hippocampal glutamate and GABA releases associated with Ca2+-induced Ca2+ releasing systems.

Recent clinical and basic studies have demonstrated that hyperactivation of interleukin-1beta (IL-1beta) plays important roles in generation of febrile and epileptic seizures. To clarify this mechanism, the present study determined the effects of IL-1beta on Ca2+-associated releases of glutamate and GABA in mouse hippocampus. Both basal and K+-evoked GABA releases were regulated by Ca2+ influx and Ca2+-induced Ca2+ releasing system (CICR). The K+-evoked glutamate release was also regulated by Ca2+ influx and CICR, whereas basal glutamate release was not affected by them. IL-1beta increased basal releases of glutamate and GABA depending on the activation of Ca2+ influx and ryanodine receptor (RyR)-sensitive CICR, but reduced K+-evoked releases depending on Ca2+ influx, RyR-sensitive and inositol 1,4,5-trisphosphate receptor (IP3R)-sensitive CICRs. During neuronal hyperexcitability, the effect of IL-1beta on GABA release was more predominantly modulated by Ca2+ influx and RyR-sensitive CICR than that on glutamate. These results indicate that hyperactivation of IL-1beta leads to imbalance between glutamatergic and GABAergic transmission via toxic overload response of Ca2+ influx and CICR.

Animals↗
PubMed2006

Involvement of Ca(2+)-induced Ca2+ releasing system in interleukin-1beta-associated adenosine release.

Interleukin-1beta (IL-1beta) plays an important role in neuroprotective and neurodegenerative events in the central nervous system. To clarify the mechanism of controversial actions of IL-1beta, we determined the effect of IL-1beta, as well as the interaction between IL-1beta and Ca(2+)-induced Ca2+ releasing system (CICR), on adenosine releases in mice hippocampus using mini-slices method. Basal and K(+)-stimulated adenosine releases were regulated by two types of CICRs, including inositol-1,4,5-trisphosphate (IP3) receptor and ryanodine receptor. Lower concentration of IL-1beta increased both adenosine releases, whereas higher concentration did not affect their releases. The stimulatory effect of IL-1beta on basal adenosine release was reduced by removal of extracellular Ca2+ and IP3 receptor inhibitor, while the stimulatory effect of IL-1beta on K(+)-stimulated adenosine release was reduced by ryanodine receptor inhibitor. These results suggest that the potent effect of IL-1beta upon adenosine release might contribute to the neuroprotective action of IL-1beta, whereas IL-1beta-induced neurodegeneration might be due to the overload response of Ca2+ mobilization and the inactivation of adenosine exocytosis.

Adenosine↗
PubMed2006

Interleukin-1beta enhances the angiotensin-induced expression of plasminogen activator inhibitor-1 through angiotensin receptor upregulation in human astrocytes.

Plasminogen activator inhibitor-1 (PAI-1) regulates not only fibrinolysis but extracellular matrix remodeling, and angiotensin II is known to play an important role in controlling the expression of PAI-1 in astrocytes. We have studied the effect of interleukin-1beta (IL-1beta), one of major cytokines also active in the nervous system, on the angiotensin II-induced expression of PAI-1 in human astrocytes. Cultures of normal human astrocytes were stimulated with IL-1beta and angiotensin II, and the expression of mRNAs for angiotensin II type 1 receptor (AT1) and PAI-1 was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) or real-time quantitative PCR. PAI-1 protein in astrocyte-conditioned medium was measured by enzyme-linked immunosorbent assay (ELISA). IL-1beta enhanced the expression of AT1 in astrocytes in time- and concentration-dependent manners. After 24-h stimulation, 10 ng/ml IL-1beta and 10 nM angiotensin II increased the levels of PAI-1 protein in astrocyte-conditioned medium by 1.9-fold and 1.8-fold of the basal value, respectively. There was no synergistic effect when the cells were stimulated simultaneously with IL-1beta and angiotensin II. When the cells were stimulated, with angiotensin II, 16 h after the stimulation with IL-1beta, the production of PAI-1 was enhanced by 1.4-fold as compared to the cells stimulated only with IL-1beta. CV-11794, an AT1 antagonist, inhibited the enhanced PAI-1 production in response to angiotensin II. We conclude that IL-1beta increases angiotensin II-induced PAI-1 secretion by astrocytes through the induction of AT1, and the enhanced secretion of PAI-1 may modulate functions of plasminogen activators in the nervous system.

Angiotensin II↗
PubMed2006

Relationship among alpha-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra.

The histologic hallmark of Parkinson disease (PD) is loss of pigmented neurons in the substantia nigra (SN) and locus ceruleus (LC) with accumulation of alpha-synuclein (alphaS). It has been reported that tyrosine hydroxylase (TH)-negative pigmented neurons are present in these nuclei of patients with PD. However, the relationship between TH immunoreactivity and alphaS accumulation remains uncertain. We immunohistochemically examined the SN and LC from patients with PD (n = 10) and control subjects (n = 7). A correlation study indicated a close relationship among decreased TH immunoreactivity, alphaS accumulation, and neuronal loss. In addition, 10% of pigmented neurons in the SN and 54.9% of those in the LC contained abnormal alphaS aggregates. Moreover, 82.3% of pigmented neurons bearing alphaS aggregates in the SN and 39.2% of those in the LC lacked TH immunoreactivity, suggesting that pigmented neurons in the SN have a greater tendency to lack TH activity than those in the LC. Recent studies have shown that this decrease of TH activity leads to a decrease of cytotoxic substances and that decreased dopamine synthesis leads to a reduction of cytotoxic alphaS oligomers. Therefore, the decrease of TH immunoreactivity in pigmented neurons demonstrated here can be considered to represent a cytoprotective mechanism in PD.

Aged↗
PubMed2006

Listeria monocytogenes induces the expression of retinoic acid-inducible gene-I.

Retinoic acid-inducible gene-I (RIG-I) is considered to play a role in innate immunity against virus infections. We showed by immunohistochemical study that RIG-I expression is upregulated in vivo in hepatic Kupffer cells and in splenic reticular cells of mice infected with Listeria monocytogenes. Both heat-killed L. monocytogenes and live L. monocytogenes induced the expression of RIG-I in cultured RAW264.7 murine macrophage-like cells in vitro. RIG-I may also be involved in innate immunity against Listeria infection.

Animals↗
PubMed2006

Oligodendrocytes within astrocytes ("emperipolesis") in the cerebral white matter in hepatic and hypoglycemic encephalopathy.

We report the occurrence of oligodendrocytes within astrocytes ("emperipolesis") in two autopsy cases of metabolic encephalopathy: one patient with hepatic encephalopathy due to citrullinemia who suffered recurrent unconsciousness (clinical duration, 32 months) and another with hypoglycemic encephalopathy who lapsed into a persistent vegetative state (clinical duration, 22 months). In both cases, hypertrophic astrocytes were found to have engulfed one to several oligodendrocytes in the devastated cerebral white matter. Previous studies have reported that emperipolesis occurs in various CNS diseases showing destruction of myelin or inflammation of the white matter, including multiple sclerosis, cerebral infarct and CJD. The present findings suggest that emperipolesis can occur even in chronic metabolic disorders that extensively involve the cerebral white matter.

Aged↗
PubMed2006

Co-localization of beta-peptide and phosphorylated tau in astrocytes in a patient with corticobasal degeneration.

The co-localization of amyloid beta (Abeta) and phosphorylated tau in astrocytes in a patient with corticobasal degeneration is described. At autopsy, the present case exhibited neuropathological findings compatible with those of corticobasal degeneration, including atrophy of the frontal and temporal lobes, neuronal loss and gliosis in the cortical and subcortical regions, and presence of cortical ballooned neurons and astrocytic plaques. Moreover, many senile plaques were found in the cerebral cortex. There were also clusters of Abeta-positive granules associated with astrocytic cytoplasm and processes in the subiculum and entorhinal cortex. In the entorhinal cortex, the Abeta-positive granules were occasionally co-localized with phosphorylated tau-positive fibrillary structures in the astrocytic cytoplasm. To our knowledge, this is the first demonstration of co-localization of Abeta and phosphorylated tau in astrocytes. This phenomenon implies that phagocytosis of Abeta coincides with production of phosphorylated tau in the same reactive astrocytes.

Amyloid beta-Peptides↗
PubMed2006

Hypoglycemic encephalopathy with extensive lesions in the cerebral white matter.

Here we report an autopsy case of hypoglycemic encephalopathy with prolonged coma. Laboratory data obtained when the patient lapsed into a coma showed that she had a low level of serum glucose (27 mg/dL). Although the level of glucose returned to within the normal range rapidly after glucose infusion, the patient remained in a coma for 22 months. It was presumed that the state of hypoglycemia persisted for about 4 h. There was no evidence of hypotension or hypoxia. Magnetic resonance imaging was performed 3 h after glucose administration; diffusion-weighted images revealed hyperintensity in the cerebral white matter and in the boundary zone between the middle and posterior cerebral arteries. Post-mortem examination revealed superficial laminar necrosis throughout the cerebral cortex. Neuronal necrosis was also found in the hippocampus and dentate gyrus, although the CA3 region appeared normal. In addition to these lesions, which are consistent with hypoglycemia-induced brain damage, the cerebral white matter exhibited severe loss of myelin and axons with reactive astrocytosis and macrophage infiltration. Old infarcts were also present in the bilateral occipital lobes. Since the cerebral blood flow is reported to be decreased during severe hypoglycemia, the present findings suggest that white matter lesions and boundary-zone infarctions may develop primarily in uncomplicated hypoglycemia.

Aged↗
PubMed2006

Cellular pathology in multiple system atrophy.

Multiple system atrophy (MSA) is a sporadic, adult-onset neurodegenerative disease, which is characterized by striatonigral degeneration, olivopontocerebellar atrophy, and preganglionic autonomic lesions in any combination. The histological hallmark is the presence of argyrophilic fibrillary inclusions in the oligodendrocytes, referred to as glial cytoplasmic inclusions (GCIs). Fibrillary inclusions are also found in the neuronal somata, axons, and nucleus. Neuronal cytoplasmic inclusions are frequently found in the pontine and inferior olivary nuclei. Since the discovery of alpha-synuclein as a major component of glial and neuronal inclusions in MSA, two neurodegenerative processes have been considered in this disease: one is due to the widespread occurrence of GCIs associated with oligodendroglia-myelin degeneration (oligodendrogliopathy) in the central nervous system, and the other is due to the filamentous aggregation of alpha-synuclein in the neurons in several brain regions. These two degenerative processes might synergistically cause neuronal depletion in MSA.

Animals↗
PubMed2006

NUB1 suppresses the formation of Lewy body-like inclusions by proteasomal degradation of synphilin-1.

NUB1 is a potent down-regulator of the ubiquitin-like protein NEDD8, because it targets NEDD8 to the proteasome for proteolytic degradation. From results in this study, we found that NUB1 physically interacts with synphilin-1 through its NEDD8-binding site, implying that NUB1 also targets synphilin-1 to the proteasome for degradation. Synphilin-1 is a major component of inclusion bodies found in the brains of patients with neurodegenerative alpha-synucleinopathies, including Parkinson's disease. In this study, we immunostained sections of brains from patients with Parkinson's disease and other alpha-synucleinopathies and demonstrated that NUB1, as well as synphilin-1, accumulates in the inclusion bodies. To define the role of NUB1 in the formation of these inclusion bodies, we performed a co-transfection assay using cultured HEK293 cells. This assay showed that NUB1 suppresses the formation of synphilin-1-positive inclusions. Further, biochemical assays revealed that NUB1 overexpression leads to the proteasomal degradation of synphilin-1. These results and our previous observations suggest that NUB1 indeed targets synphilin-1 to the proteasome for its efficient degradation, which, because of the resultant reduction in synphilin-1, suppresses the formation of synphilin-1-positive inclusions.

Adaptor Proteins, Signal Transducing↗
PubMed2005

An autopsy case of early ("minimal change") olivopontocerebellar atrophy (multiple system atrophy-cerebellar).

We report a 57-year-old woman with multiple system atrophy (MSA) of 15-month duration. The patient developed dysarthria, followed by impaired balance of gait, mild limb ataxia, and saccadic eye movement. A postmortem examination performed after she was found dead in a bathtub revealed neuronal loss restricted to the olivopontocerebellar system, being more severe in the pontine nucleus. Mild neuronal loss was also found in the anterior vermis and inferior olivary nucleus. Alpha-synuclein immunohistochemistry demonstrated widespread occurrence of glial cytoplasmic inclusions in the central nervous system, which were more numerous in the pontine base and cerebellar white matter. In contrast, neuronal alpha-synuclein accumulation was confined to the pontine and inferior olivary nuclei. The number of neuronal intranuclear inclusions was much higher than that of neuronal cytoplasmic inclusions. Moreover, alpha-synuclein accumulation was more severe in the neurites than in the cytoplasm or nucleus. This case demonstrates the early pattern of brain pathology in MSA-cerebellar (olivopontocerebellar atrophy).

Brain↗
PubMed2005

Cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy body disease.

Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [123I]MIBG myocardial scintigraphy has been reported in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We hypothesized that cardiac sympathetic denervation might account for the pathomechanism. To elucidate the extent, frequency and pattern of cardiac sympathetic nerve involvement in Lewy body disease and related neurodegenerative disorders, we immunohistochemically examined heart tissues from patients with PD (n=11), DLB (n=7), DLB with Alzheimer's disease (DLB/AD; n=4), multiple system atrophy (MSA; n=8), progressive supranuclear palsy (PSP; n=5), pure AD (n=10) and control subjects (n=5) together with sympathetic ganglia from patients with PD (n=5) and control subjects (n=4), using an antibody against tyrosine hydroxylase (TH). TH-immunoreactive nerve fibers in the hearts had almost entirely disappeared in nearly all the patients with PD, DLB and DLB/AD, whereas they were well preserved in all the patients with PSP and pure AD as well as in all except for one patient with MSA. In PD, neurons in the sympathetic ganglia were preserved in all except for one patient. Decreased cardiac uptake of MIBG in Lewy body disease reflects actual cardiac sympathetic denervation, which precedes the neuronal loss in the sympathetic ganglia.

3-Iodobenzylguanidine↗
PubMed2005

Preserved cardiac sympathetic nerve accounts for normal cardiac uptake of MIBG in PARK2.

We performed [123I] MIBG myocardial scintigraphy in two of three patients with PARK2 from unrelated families and examined the heart tissues from the three patients immunohistochemically using an antibody against tyrosine hydroxylase (TH) to see whether cardiac sympathetic nerve is involved. Cardiac uptake of MIBG was normal except for a slight decrease in the late phase in one of the patients. Postmortem examination revealed that TH-immunoreactive nerve fibers in the epicardium were well preserved in all three patients. The present study confirmed that cardiac sympathetic nerve is well preserved in PARK2 with a homozygous exon deletion, which accounts for normal cardiac uptake of MIBG. Moreover, normal cardiac uptake of MIBG might be of potential diagnostic value to indicate the absence of Lewy body pathology, even in patients with levodopa-responsive Parkinsonism, as in PARK2.

3-Iodobenzylguanidine↗
PubMed2005

Effects of ryanodine receptor activation on neurotransmitter release and neuronal cell death following kainic acid-induced status epilepticus.

Dynamic changes in intracellular free Ca(2+) concentration play a crucial role in various neural functions. The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) and the ryanodine (Ry) receptor (RyR) are involved in Ca(2+)-induced Ca(2+)-release (CICR). Recent studies have shown that type 3 IP3R is highly expressed in rat hippocampal neurons after kainic acid (KA)-induced seizures and that dantrolene, a RyR antagonist, reduces KA-induced neuronal cell death. We investigated the RyR-associated effects of CICR agents on basal and K(+)-evoked releases of GABA and glutamate in rat hippocampus and the changes in expression of mRNA for RyRs in mouse brain after KA-induced seizures. The stimulatory effect of Ry on releases of GABA and glutamate was concentration-dependent in a biphasic manner. The inflection point in concentration-response curves for Ry on GABA release was lower than that for glutamate in both basal and K(+)-evoked conditions, suggesting that hyperactivation of RyR-associated CICR produces the imbalance between GABAergic and glutamatergic transmission. Following KA-induced seizures, transient up-regulation of brain-type RyR mRNA was observed in the hippocampal CA3 region and striatum, and signals for c-Fos mRNA increased transiently in the hippocampus, dentate gyrus and deeper layers of the neocortex. Thereafter, some dead neurons with single-stranded DNA (ssDNA) immunoreactive fragmented nuclei appeared in these areas. These findings suggest that intracellular Ca(2+) release via the RyR might be one of the mechanisms involved in KA-induced neuronal cell death.

Animals↗
PubMed2005

Peculiar venous lesions in fatal hyponatremic brain edema.

A 19-year-old woman with a 3-year history of schizophrenia suddenly began to vomit, and rapidly developed a coma an hour after the onset of vomiting. A brain CT scan showed diffuse brain edema with compression of the ventricles. Laboratory tests showed a low serum sodium concentration of 117 mmol/L. She died 67 h after the onset of the first symptom. A postmortem examination showed diffuse swelling of the brain with bilateral uncal and tonsillar herniations. Histologically, no necrotic, hemorrhagic or encephalitic changes were seen. However, microvacuolar changes with lymphocytic infiltration were found in the venous walls (media and adventitia) mainly in the basal ganglia, thalamus and brainstem. To our knowledge, this is the first demonstration of venous alterations in fatal hyponatremic brain edema. These changes may have participated in the exacerbation of the brain edema due to functional disturbance of venous drainage.

Adult↗
PubMed2005

Disseminated intraparenchymal microgranulomas in the brainstem in central nervous system sarcoidosis.

We report a 70-year-old woman with sarcoidosis and multiple cranial nerve palsy. The patient suffered from dysarthria, dysphagia and weakness of the upper and lower extremities and died of sepsis. No abnormalities were noted in brain MRI. At autopsy, numerous epithelioid granulomas with Langhans giant cells were present in the bilateral lungs, including the hilar lymph nodes. The brain had a normal external appearance. Histologically, there were brainstem parenchymal lesions consisting of many microgranulomas, lymphocytic infiltration, activated microglias and astrocytosis. Perivascular lympocytic cuffing was also seen. Neither granulomas nor lymphocytic infiltration were seen in the leptomeninges. The present case was considered to be a peculiar type of neurosarcoidosis, that is, "sarcoid brainstem encephalitis".

Aged↗