BACKGROUND AND PURPOSECilostazol may be effective in dementia associated with a cerebral ischaemia. In this study, we examined whether it exerts beneficial effects on learning and/or memory impairment induced by Ab25-35 in mice, and compared its effects with those of aspirin. EXPERIMENTAL APPROACHAb25-35 (9 nmol) was administered to mice i.c.v. Learning and memory behaviour were evaluated by measuring spontaneous alternation in a Y-maze and a step-down type passive avoidance test, on the 5th and 8th days after injection respectively. Levels of lipid peroxidation (malondialdehyde) and cytokines in the frontal cortex and hippocampus were measured 2, 3, 5 and 7 days after the Ab25-35 injection. The effects of repeated administration of cilostazol and aspirin (both at 30 and 100 mg·kg -1 , p.o.) on any changes induced by Ab25-35 were evaluated. KEY RESULTSRepeated administration of cilostazol significantly attenuated the impairment of spontaneous alternation and the shortened step-down latency induced by Ab25-35. Aspirin did not show any beneficial effect. A significant increase in the levels of malondialdehyde (MDA) and IL-1b (only measured in hippocampus) was observed 2, 3 and 5 days after the Ab25-35 injection in the frontal cortex and hippocampus. Repeated administration of cilostazol (100 mg·kg -1 ) completely prevented the increase in MDA levels but failed to antagonize the increase in the expression of IL-1b induced by Ab25-35. CONCLUSIONS AND IMPLICATIONSThese results suggest that the protective effect of cilostazol on Ab25-35-induced memory impairment may be related to oxidative stress in the frontal cortex and the hippocampus. AbbreviationsAb, amyloid b; AD, Alzheimer's disease; APP, amyloid precursor protein; BACE, b-site of amyloid precursor protein cleaving enzyme; CMC, carboxymethyl cellulose sodium salt; CREB, cAMP-responsive element binding protein cilostazol:6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)

No abstract

The reaction of the terminal dithiol complex trans-[(RhCp*)2(μ-CH2)2(SH)2] (1, Cp* = η5-C5Me5) with dialkyl acetylenedicarboxylate gives the terminal bis(ethenethiolate) complex trans-[(RhCp*)2(μ-CH2)2(SCR1CHR2)2] (2a, R1, R2 = COOMe; 2b, R1, R2 = COOEt). Treatment of the cationic bridging thiol complex [(RhCp*)2(μ-CH2)2(μ-SH)](BPh4) (3) with dimethyl acetylenedicarboxylate or carbyl propiolate very easily gives the bridging ethenethiolate complex [(RhCp*)2(μ-CH2)2(μ-SCR1CHR2)](BPh4) (4a, R1, R2 = COOMe; 4b, R1 = H, R2 = COOPh; 4c, R1 = H, R2 = COOMe). Although complex 2 is not able to react further with alkyne, complex 4 does and forms the butadiene complex [(RhCp*)2(η2:η2-μ-CH2CR3CR4CH2)(μ-SCR1CHR2)](BPh4) (5a, R1, R2, R3, R4 = COOMe; 5a-Et 2 , R1, R2 = COOMe, R3, R4 = COOEt; 5a-Et 1 , R1, R2 = COOMe, R3 = H, R4 = COOEt; 5b, R1 = H, R2 = COOPh, R3, R4 = COOMe; 5c, R1 = H, R2 = COOMe, R3, R4 = COOMe). The structures of complexes 2b, 4a, and 5a have been confirmed by an X-ray diffraction study.

Heterotrimeric G proteins are the molecule switch that transmits information from external signals to intracellular target proteins in mammals and yeast cells. In higher plants, heterotrimeric G proteins regulate plant architecture. Rice harbors one canonical α subunit gene (RGA1), four extra-large GTP-binding protein genes (XLGs), one canonical β-subunit gene (RGB1), and five γ-subunit genes (tentatively designated RGG1, RGG2, RGG3/GS3/Mi/OsGGC1, RGG4/DEP1/DN1/qPE9-1/OsGGC3, and RGG5/OsGGC2) as components of the heterotrimeric G protein complex. Among the five γ-subunit genes, RGG1 encodes the canonical γ-subunit, RGG2 encodes a plant-specific type of γ-subunit with additional amino acid residues at the N-terminus, and the remaining three γ-subunit genes encode atypical γ-subunits with cysteine-rich C-termini. We characterized the RGG4/DEP1/DN1/qPE9-1/OsGGC3 gene product Gγ4 in the wild type (WT) and truncated protein Gγ4∆Cys in the RGG4/DEP1/DN1/qPE9-1/OsGGC3 mutant, Dn1-1, as littele information regarding the native Gγ4 and Gγ4∆Cys proteins is currently available. Based on liquid chromatography-tandem mass spectrometry analysis, immunoprecipitated Gγ4 candidates were confirmed as actual Gγ4. Similar to α-(Gα) and β-subunits (Gβ), Gγ4 was enriched in the plasma membrane fraction and accumulated in the developing leaf sheath. As RGG4/DEP1/DN1/qPE9-1/OsGGC3 mutants exhibited dwarfism, tissues that accumulated Gγ4 corresponded to the abnormal tissues observed in RGG4/DEP1/DN1/qPE9-1/OsGGC3 mutants.