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Volume 115 (2000)
- Issue 6 Pages 323-
- Issue 5 Pages 271-
- Issue 4 Pages 185-
- Issue 3 Pages 123-
- Issue 2 Pages 67-
- Issue 1 Pages 5-
Volume 115, Issue 2
Displaying 1-5 of 5 articles from this issue
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Isao KANEKO, Takekazu KUBO, Kiyoshi MORIMOTO2000 Volume 115 Issue 2 Pages 67-77
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSRecent observations on the neurotoxicity of β-amyloid have been reviewed and possible roles of racemization of β-amyloid are discussed. β1-40, β25-35 and D-Ser26β25-35 (all HCl salt forms), but not commercially available β1-40 (TFA salt form), take the β-structure within few hours in PBS, form fibrils, exert toxic effects on hippocampal cultured neurons and suppresses MTT reduction activity of non-neuronal HeLa cells without cytotoxicity. D-Ser26β1-40 is soluble and non-toxic in vitro but is converted by brain proteinases to D-Ser26β25-35, a potent toxic and proteinase-resistant fragment. The co-injection of β1-40, D-Ser26β25-35 or D-Ser26β1-40 with ibotenic acid, but not β-amyloid alone or ibotenic acid alone, into rat brains produce drastic neuronal loss in the hippocampal CA1 area. The in vivo degeneration activity of β-amyloids is well correlated with their having β-structure and activity to suppress the MTT reduction activity. A specific antibody against D-Ser26β25-35 strongly reacts with hippocampal degenerated-CA1 neurons in AD but not control brains. These results suggest that D-Ser26β25-35 and related peptides possibly generated from insoluble β1-40 due to aging exert toxic effects on the hippocampal CA1 pyramidal neurons by enhancing the susceptibility to excitatory amino acids.View full abstractDownload PDF (12824K) -
Masatoshi TAKEDA, Kazuhiro SHINOSAKI, Takashi NISHIKAWA, Toshihisa TAN ...2000 Volume 115 Issue 2 Pages 79-88
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSRecent advances in the knowledge about Alzheimer pathogenesis indicate several tactics for the development of drugs to treat Alzheimer's disease. Firstly, the function of presenilin, the causative gene for most familial Alzheimer's disease, has been demonstrated to be the protease in the Notch signaling system. Pre-senilin cleaves the transmembrane domain of the C-terminal fragment of the Notch-1 molecule, which is generated by proteolysis by furin-like proteases. APP is also cleaved by presenilin at the γcut site, implying that presenilin is γ-secretase itself or at least closely functioning with γ-secretase. A recent paper has demonstrated that immunization of APP transgenic mouse with amyloid β42 may decrease and prevent amyloid deposition in brain tissue. This unique and novel approach may open the new tactics for developing anti-dementia drugs. Another important finding comes from the identification of the function of prolyl isomerase. It is demonstrated that pin 1, intra-nuclear prolyl isomerase, can restore the microtubule binding capacity of phosphorylated tau, which clearly shows a solid strategy for developing drugs for preventing neuronal degeneration.View full abstractDownload PDF (11892K) -
Hiroaki HISA2000 Volume 115 Issue 2 Pages 89-98
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSThe kidney plays a pivotal role in cardiovascular homeostasis through control of extracellular fluid volume, the mechanisms of which have been studied in detail at both cellular and molecular levels in each portion of the kidney. Renal clearance experiments in vivo are useful for analyzing renal functions as the integrated system of vascular, glomerular and tubular components. Physiological responses and drug effects within the kidney can be more clearly analyzed by measuring renal release of endogenous substances and by applying intrarenal arterial drug administration. For example, our recent studies in anesthetized dogs revealed the participation of phosphodiesterase IV in regulation of renal cAMP level and the influences by changes in renal cAMP level on renal hemodynamics, glomerular filtration and tubular reabsorption. The in vivo experiments also allow us to evaluate a sequence of events in the neural control of renal functions. We observed that an adenylate cyclase activator counteracted hypofiltration to attenuate antinatriuresis during sympathetic activation without inhibiting neurotransmitter release. The experiments in the in vivo kidney, although they provide only indirect information on intracellular events, are necessary for understanding the total renal functions and could thereby contribute to physiology and pharmacology of the cardiovascular system.View full abstractDownload PDF (11484K) -
Kiyofumi YAMADA, Toshitaka NABESHIMA2000 Volume 115 Issue 2 Pages 99-104
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSNitric oxide (NO) is a free radical gas with a role in signal transduction in diverse processes. In the central nervous system, NO acts as an intercellular signaling molecule as well as a neurotoxic substance. To clarify the role of NO in the brain, we measured nitrite and nitrate levels, as indices of NO production, in the dialysate of brains in conscious rats, by using an in vivo dialysis technique. We have demonstrated that NO production in the cerebellum can be modulated by the activation of glutamate receptors and KCl stimulation. Glial cells appear to be involved in the modulation of NO production by regulating the availability of an NO precursor, L-arginine. We have also demonstrated that NO plays a role in the development of lipopolysaccharide-induced brain dysfunction and pentylenetetrazol-induced kindling. We believe that the in vivo dialysis method to measure nitrite and nitrate levels as indices of NO production is a useful tool for investigating physiological and pathophysiological roles of NO in the brain.View full abstractDownload PDF (5420K) -
[in Japanese]2000 Volume 115 Issue 2 Pages 107-109
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSDownload PDF (3037K)
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