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Biomedical subjects

Akira Monji

Publications and source records attributed to Akira Monji.

At least 19 recordsLinked to original sources
PubMed2006

Phospholipids modulate superoxide and nitric oxide production by lipopolysaccharide and phorbol 12-myristate-13-acetate-activated microglia.

Microglial activation and inflammatory processes have been implicated in the pathogenesis of a number of neurodegenerative disorders. Recently, peroxynitrite (ONOO(-)), the reaction product of superoxide (O(2)(-)) and nitric oxide (NO) both of which can be generated by activated microglia, has been demonstrated to act as a major mediator in the neurotoxicity induced by activated microglia. On the other hand, phospholipids such as phosphatidylserine (PS) and phosphatidylcholine (PC) have been reported to modulate the immune function of phagocytes. We therefore evaluated the effects of liposomes which comprise both PS and PC (PS/PC liposomes) or PC only (PC liposomes) regarding the production of both O(2)(-) and NO by lipopolysaccharide (LPS)/phorbol 12-myristate-13-acetate (PMA)-activated microglia using electron spin resonance (ESR) spin trap technique with a DEPMPO and Griess reaction, respectively. Pretreatment with PS/PC liposomes or PC liposomes considerably inhibited the signal intensity of O(2)(-) adduct associated with LPS/PMA-activated microglia in a dose-dependent manner. In addition, pretreatment with PS/PC liposomes also significantly reduced LPS/PMA-induced microglial NO production. In contrast, pretreatment with PC liposomes had no effect on the NO production. These results indicate that PS/PC liposomes can inhibit the microglial production of both NO and O(2)(-), and thus presumably prevent a subsequent formation of ONOO(-). Therefore, PS/PC liposomes appear to have both neuroprotective and anti-oxidative properties through the inhibition of microglial activation.

Animals↗
PubMed2006

Amyloid formation in denatured single-mutant lysozymes where residual structures are modulated.

Reduced hen lysozyme has a residual structure involving long-range interaction. It has been demonstrated that a single mutation (A9G, W62G, W111G, or W123G) in the residual structure differently modulates the long-range interactions of reduced lysozyme. To examine whether such variations in the residual structure affect amyloid formation, reduced and alkylated mutant lysozymes were incubated under the amyloid-fibrillation condition. From the analyses of CD spectra and thioflavine T fluorescences, it was suggested that variation in residual structure led to different amyloid formation. Interestingly, the extent of amyloid formation did not always correlate with the extent to which the residual structure was maintained, resulting in the involvement of a hydrophobic cluster normally contained in W111 in the reduced lysozyme.

Amyloid↗
PubMed2006

Different SPECT findings before and after Capgras' syndrome in interictal psychosis.

We herein report a case of Capgras' syndrome observed in interictal psychosis in which the single-photon emission computed tomography (SPECT) findings before and after the appearance of the psychotic symptoms differed. SPECT with 99mTc-hexamethyl propyleneamine oxine (HMPAO) revealed worsening of hypoperfusion in the entire right hemisphere after onset of the psychotic symptoms. The enhanced hypoperfusion demonstrated by SPECT in the present case seems to indicate a right interhemispheric disconnection resulting in the occurrence of Capgras' syndrome.

Adult↗
PubMed2006

Depletion of intracellular Ca2+ store itself may be a major factor in thapsigargin-induced ER stress and apoptosis in PC12 cells.

The mechanisms of intracellular calcium store depletion and store-related Ca(2+) dysregulation in relation to apoptotic cell death in PC12 cells were investigated at physiological temperatures with a leak-resistant fluorescent indicator dye Fura-PE3/AM by a cooled CCD imaging analysis system. Electron microscopic observations have shown thapsigargin (TG; 100 nM)-induced apoptosis in PC12 cells. Thorough starvation of stored Ca(2+) by BAPTA/AM (50 microM), or La(3+) (100 microM) enhanced while dantrolene (100 microM) attenuated the TG-induced apoptosis by preventing a calcium release from internal stores. An immunoblotting analysis revealed an enhanced expression of GRP78, the hallmark of endoplasmic reticulum (ER) stress when cells were treated by TG along with BAPTA/AM. These results indicate that the depletion of the intracellular Ca(2+) stores itself induces the ER stress and apoptosis in PC12 cells without any involvement of the capacitative calcium entry (CCE) or a sustained elevation of intracellular Ca(2+) concentrations ([Ca(2+)](i)).

Animals↗
PubMed2005

Amyloid-beta fibril formation is not necessarily required for microglial activation by the peptides.

There is increasing evidence that microglial activation has pathogenic influence on Alzheimer's disease. According to in vitro studies, microglia activated by amyloid-beta (Abeta) peptides have been reported to damage or kill neurons by the release of neurotoxic molecules such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, nitric oxide or reactive oxygen species. Although the relationship between the aggregational state of Abeta peptides and their neurotoxic activities has been well investigated, little is known about the relationship between the aggregational state of Abeta peptides and their ability to induce microglial activation. In the present study, we thus performed both structural and biochemical studies to clarify the relationship between the aggregational state of Abeta peptides and their ability to activate microglia. Our results have shown that, in the presence of interferon-gamma, the Abeta25-35(M(35)Nle) peptide had almost the same potency of activating microglia and producing TNF-alpha as the Abeta25-35 peptide on both protein and mRNA levels, in spite of the fact that former peptide represented much less amyloid fibril formation than the latter in a thioflavine-T fluorometric assay. These results suggest that Abeta fibril formation is not necessarily required for microglial activation by the peptides.

Alzheimer Disease↗
PubMed2005

Plasma folate and homocysteine levels may be related to interictal "schizophrenia-like" psychosis in patients with epilepsy.

Genetic and clinical data suggest that folate and homocysteine may play a role in the pathogenesis of psychiatric disorders. The total plasma homocysteine level is a sensitive measure of a functional folate deficiency. We thus investigated whether a functional folate deficiency and/or elevated levels of plasma homocysteine may be related to interictal "schizophrenia-like" psychosis (interictal psychosis ) of epilepsy. We studied the plasma folate, vitamin B12, and homocysteine levels of 32 age- and sex-matched epileptic patients with or without interictal psychosis. Each group included 25 localization-related epilepsies and 7 generalized epilepsies. The epileptic patients with interictal psychosis had significantly lower folate levels and higher homocysteine levels than those without interictal psychosis. There were no significant differences in the vitamin B12 levels between the two groups. The present study suggests that low plasma folate and high plasma homocysteine levels may be related to the pathophysiology of interictal psychosis of epilepsy. In future studies, we should investigate whether folate supplementation, in addition to antipsychotics, might play a beneficial role in the treatment of interictal psychosis in epileptic patients. Furthermore, the present findings should be confirmed by prospective longitudinal studies in a larger group of patients with epilepsy.

Adult↗
PubMed2005

Aluminum chloride does not facilitate deposition of human synthetic amyloid beta1-42 peptide in the rat ventricular system of a short-term infusion model.

Recent data have demonstrated that a 39-43 amino acid peptide called beta-amyloid peptide (Abeta), which predominantly contains 42 residues (Abeta1-42), has a strong tendency to form insoluble aggregates and that the toxic effects of Abeta are based on its aggregation. In a previous study, we reported that infusion of 100 microg of human synthetic Abeta1-42 (sAbeta1-42), which is a main component of diffuse plaques, into the lateral ventricle of the rat brain of a short-term infusion model resulted in almost complete disappearance of sAbeta1-42 aggregates from the ventricles by 28 days. In addition, aluminum is considered a potential etiological factor in Alzheimer's disease (AD). Neurotoxicity from excess brain exposure to aluminum has been documented from both clinical observations and animal experiments, although a direct relationship between aluminum and AD has yet to be clearly established. We therefore investigated the effects of sAbeta1-42 aggregates with aluminum chloride (AlCl3) in the ventricular system of the rat brain of a short-term infusion model. At either 2 or 7 days following infusion, sAbeta1-42 formed aggregates with AlCl3 that spread throughout the entire ventricular system. However, sAbeta1-42 aggregates with AlCl3 had almost disappeared from the ventricles by 28 days, resulting in similarities with respect to the time-course and the neuropathological changes observed in sAbeta1-42 aggregation without AlCl3. We herein report for the first time that considerable amounts of sAbeta1-42 aggregates with AlCl3 almost disappear from the rat ventricular system by 28 days post-infusion.

Aluminum Chloride↗
PubMed2002

Amyloid-beta-protein (A beta) (25-35)-associated free radical generation is strongly influenced by the aggregational state of the peptides.

We investigated whether or not the Amyloid-beta-protein (A beta) itself spontaneously generates free radicals using electron spin resonance (ESR) spectroscopy while also monitoring the aggregational state of A beta and A beta-induced cytotoxicity. The present results demonstrated a four-line spectrum in the presence of A beta25-35 with N-tert-butyl-alpha-phenylnitrone (PBN) but not in the presence of PBN alone in phosphate-buffered saline (PBS). The fact that the four-line spectrum obtained for the A beta25-35/PBN in PBS was completely abolished in the presence of the iron-chelating agent Desferal demonstrated the observed four-line spectrum to be iron-dependent. On the other hand, A beta25-35 with PBN in phosphate buffer (PB) did not produce any definite four-line spectrum. the present results showed the amyloid fibril formation of A beta25-35 in PBS to be much higher than that of A beta25-35 in PB. Moreover, A beta-induced cytotoxicity assays showed A beta incubated in PBS to be more cytotoxic than that incubated in PB. These results thus demonstrate that A beta(25-35)-associated free radical generation is strongly influenced by the aggregational state of the peptides.

Alzheimer Disease↗
PubMed2002

Brain-derived neurotrophic factor induces long-lasting Ca2+-activated K+ currents in rat visual cortex neurons.

Brain-derived neurotrophic factor (BDNF) increases postsynaptic intracellular Ca2+ and modulates synaptic transmission in various types of neurons. Ca2+-activated K+ currents, opened mainly by intracellular Ca2+ elevation, contribute to hyperpolarization following action potentials and modulate synaptic transmission. We asked whether BDNF induces Ca2+-activated K+ currents by postsynaptic elevation of intracellular Ca2+ in acutely dissociated visual cortex neurons of rats. Currents were analysed using the nystatin-perforated patch clamp technique and imaging of intracellular Ca2+ mobilization with fura-2. At a holding potential of -50 mV, BDNF application (20 ng/mL) for 1-2 min induced an outward current (IBDNF-OUT; 80.0 +/- 29.0 pA) lasting for more than 90 min without attenuation in every neuron tested. K252a (200 nm), an inhibitor of Trk receptor tyrosine kinase, and U73122 (3 microm), a specific phospholipase C (PLC)-gamma inhibitor, suppressed IBDNF-OUT completely. IBDNF-OUT was both charybdotoxin- (600 nm) and apamin- (300 nm) sensitive, suggesting that this current was carried by Ca2+-activated K+ channels. BAPTA-AM (150 microm) gradually suppressed IBDNF-OUT. Fura-2 imaging revealed that a brief application of BDNF elicited a long-lasting elevation of intracellular Ca2+. These results show that BDNF induces long-lasting Ca2+-activated K+ currents by sustained intracellular Ca2+ elevation in rat visual cortex neurons. While BDNF, likely acting through the Trk B receptor, was necessary for the induction of long-lasting Ca2+-activated K+ currents via intracellular Ca2+ elevation, BDNF was not necessary for the maintenance of this current.

Action Potentials↗
PubMed2002

Measurement of laminins in the cerebrospinal fluid obtained from patients with Alzheimer's disease and vascular dementia using a modified enzyme-linked immunosorbent assay.

We developed a new enzyme-linked immunosorbent assay (ELISA) system using antibodies against intact human laminin, laminin alpha(5)-chain, laminin beta(1)-chain, laminin gamma(1)-chain and laminin alpha(1)-chain peptide (YFQRYLI). Using this ELISA, we measured the anti-laminin immunoreactivity levels in the cerebrospinal fluid (CSF) obtained from patients with Alzheimer's disease (AD), vascular dementia (VaD), and other disorders. The present study showed the levels of certain laminins in CSF to demonstrate significant differences in the chain levels in different dementias. The AD group showed a significantly lower level of anti-laminin gamma(1) immunoreactivity. The late-onset AD group showed significantly elevated anti-laminin alpha(1)-peptide (YFQRYLI) immunoreactivity levels in comparison with the early-onset AD group and controls. On the other hand, the VaD group showed significantly higher levels of anti-intact human laminin and anti-laminin beta(1) immunoreactivity. The assays of anti-laminin immunoreactivity levels in CSF provided an efficient sensitivity (85.0%) and specificity (93.7%) for the diagnosis of AD by using the ratio of tau to anti-intact human laminin immunoreactivity levels. These results suggest that CSF laminin or its derivatives may correlate with the pathogenesis of AD and VaD, and the prevention of the proteolytic activity may be an effective therapeutic method for either preventing or slowing down the progression of AD. Furthermore, it was shown that performing ELISA for CSF laminins may prove to be useful for detecting the biological markers of AD and VaD.

Aged↗
PubMed2002

Effect of sucrose on formation of the beta-amyloid fibrils and D-aspartic acids in Abeta 1-42.

Beta-amyloid peptide 1-42 is a major peptide constituent of beta-amyloid fibrils. We investigated the role of sucrose on the deposition and the D-aspartic acid formation in an amyloidogenic peptide 1-42 under physiological conditions. From analyses using thioflavine-T fluorometric assay and electronmicroscopic spectroscopy after 60 h incubation at 37 degrees C, it was found that sucrose retarded the fibril formation in the amyloidogenic peptide. The retardation of the formation of amyloid fibrils by sucrose was suggested to be not due to viscosity but due to disturbance of the assemlby of alpha-helix containing peptides. Moreover, we showed that the formation of D-aspartyl residue, which is found in beta-amyloid fibrils from Alzheimer disease brains, in the amyloidogenic peptide was also retarded in the presence of sucrose.

Amyloid beta-Peptides↗