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Hideya Kawasaki

Publications and source records attributed to Hideya Kawasaki.

At least 19 recordsLinked to original sources
PubMed2006

Mode of interaction of two fluorinated-hydrogenated hybrid amphiphiles with dipalmitoylphosphatidylcholine (DPPC) at the air-water interface.

Two-component Langmuir monolayers formed on 0.02 M Tris buffer solution (pH 7.4) with 0.13 M NaCl at 298.2K were investigated for two different fluorinated-hydrogenated hybrid amphiphiles (F6PH5PPhNa and F8PH5PPhNa or F6 and F8, respectively) with DPPC. Surface pressure (pi), surface potential (DeltaV) and dipole moment (mu( perpendicular)) as a function of molecular surface area (A) were measured by employing the Whilhelmy method and an ionizing electrode method. From the A- and DeltaV-X(F6) (or X(F8)) curves, partial molecular surface area (PMA) and apparent partial molecular surface potential (APSP) were determined as a function of surface mole fraction (X(Fn)) at discrete surface pressures. Then, the behavior of occupied surface areas and surface potentials of the respective components could be made clearer. Compressibility (C(s)), elasticity (C(s)(-1)), and excess Gibbs energy (DeltaG((ex))) as a function of X(F6) (or X(F8)) were estimated at definite pressures. These physico-chemical parameters were found to reflect the mechanical strength of monolayer films formed. The regular solution theory being applied to DeltaG((ex)), the activity coefficients (f) as well as the interaction parameter (I(p)) between DPPC and two hybrid amphiphiles in the binary monolayers were evaluated. I(p) values thus obtained indicated that F8 molecules interact more strongly with DPPC molecules than F6. Moreover, in order to better understand the morphological monolayer state, Langmuir-Blodgett (LB) films made from DPPC and fluorinated-hydrogenated hybrid amphiphiles were examined by atomic force microscopy (AFM). The miscibility of the two components in the monolayer state is evidenced by these thermodynamic quantities and AFM observations. Furthermore, AFM images demonstrated that F8 could more effectively disperse the ordered domains of DPPC than F6.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2006

Mode of interaction of ganglioside Langmuir monolayer originated from echinoderms: three binary systems of ganglioside/DPPC, ganglioside/DMPE, and ganglioside/cholesterol.

The surface pressure (pi)-area (A), the surface potential (DeltaV)-A, and the dipole moment (mu( perpendicular))-A isotherms were obtained for monolayers made from a ganglioside originated from echinoderms [Diadema setosum ganglioside (DSG-1)], dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylethanolamine (DMPE), cholesterol (Ch), and their combinations. Monolayers spread on several different substrates were investigated at the air/water interface by the Wilhelmy method, ionizing electrode method, fluorescence microscopy (FM) and atomic force microscopy (AFM). Surface potentials (DeltaV) of pure components were analyzed using the three-layer model proposed by Demchak and Fort [R.J. Demchak, T. Fort, J. Colloid Interface Sci. 46 (1974) 191-202]. The new finding was that DSG-1 was stable and showed a liquid-expanded film and that its monolayer behavior of DeltaV was sensitive for the change of the NaCl concentration in the subphase. Moreover, the miscibility of DSG-1 and three major lipids in the two-component monolayers was examined by plotting the variation of the molecular area and the surface potential as a function of the DSG-1 molar fraction (X(DSG-1)), using the additivity rule. From the A-X(DSG-1) and DeltaV(m)-X(DSG-1) plots, partial molecular surface area (PMA) and apparent partial molecular surface potential (APSP) were determined at the discrete surface pressure. The PMA and APSP with the mole fraction were extensively discussed for the miscible system. The miscibility was also investigated from the two-dimensional phase diagrams. Furthermore, a regular surface mixture, for which the Joos equation was used for the analysis of the collapse pressure of two-component monolayers, allowed calculation of the interaction parameter (xi) and the interaction energy (-Deltavarepsilon) between them. The observations using fluorescence microscopy and AFM image also provide us the miscibility in the monolayer state.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2006

Reversible micelle-vesicle conversion of oleyldimethylamine oxide by pH changes.

A preliminary study on the reversible micelle-vesicle conversion of oleyldimethylamine oxide [Kawasaki, H. et al. J. Phys. Chem. B. 2002, 106, 1524 ] is extended in the present study. In the presence of 0.01 M NaCl at a surfactant concentration of 0.05 M, a micelle-to-vesicle conversion with increasing degree of ionization alpha takes place in the following sequence: growth of fibrous micelle (alpha < 0.2), a fused network (alpha approximately 0.3), fibrous micelles + (perforated) vesicles (alpha = 0.4), and vesicles + lamellae (alpha = 0.5). Viscoelasticity correspondingly varies from the Maxwell-type behavior of the entangled network of fibrous micelles to the gel-like behavior of vesicle suspensions, via a fluid solution-like behavior of the fused network. This phase sequence is in contrast with the case of no added salt where no branching of micelles is observed, and long micelles and bilayers (vesicles + lamellae) coexist at alpha = 0.5. In water, a state of the lowest viscoelasticity occurs around alpha = 0.2 for both surfactant concentrations 0.05 and 0.15 M. Synergism between protonated and nonprotonated amine oxide headgroups is observed despite low ionic strengths. From the time course of the reversible micelle-vesicle conversion, vesicles seem to be formed from threadlike micelles within 25 h according to the shear moduli, while a longer conversion time is suggested by a flow property (viscosity). Shear thickening behavior is observed at alpha = 0.2 and 0.4 in 0.01 M NaCl but not in water.

Journal Article↗
PubMed2006

Charge-induced unilamellar vesicle formation and phase separation in solutions of Di-n-decylmethylamine oxide.

A double-tail amine oxide surfactant, di-n-decylmethylamine oxide (2C10MAO), was prepared, and the effects of protonation on aggregate structure were examined by small-angle neutron scattering (SANS), cryo-transmission electron microscopy (cryo-TEM), turbidity, electric conductivity, and solubilization of an oil-soluble dye at various degrees of neutralization, X, defined as the mole ratio of HCl/2C10MAO. The surfactant makes an L(2) phase in the nonprotonated state (X = 0) in water. The L(2) phase is in equilibrium with an aqueous L(1) phase. On protonation, unilamellar vesicles (ULVs) are formed over a wide range of compositions (0.05 < X< 0.4-0.5 at C = 10 mM) as observed by cryo-TEM. At X = 0.2, the ULV is stable over a wide concentration range (3 mM < or = C < 0.1 M), but an L(alpha) phase replaces the vesicle phase at C > 0.1 M. SANS results show that the mean radius of the ULV is about 25 nm and the bilayer thickness is about 2 nm, consistent with the extended configuration of the alkyl chains of the surfactant. An important contribution to the enhanced stability of the bilayer structures over the L(2) phase is suggested to be the translational entropy of the counterions. The enhanced stability of the bilayers diminishes as the counterion concentration increases either by an increase of X or by the addition of a salt. When the counterion concentration exceeds a critical value, the ULV solutions transform into the L(2) phase (or L(2)/L(1) two-phase system at low surfactant concentrations). The critical composition X is about 0.4-0.5 in water, but it is below 0.4 in D(2)O. The critical NaCl concentration is below 5 mM at X = 0.2. The stability of ULVs against multilamellar vesicles is ascribed partly to undulation forces and partly to the adjustable nature of the spontaneous curvature of amine oxide monolayers. The characteristics of the ULV of the surfactant remain the same within a temperature range 25-50 degrees C at X = 0.2. An iridescent lamellar phase and possibly an L(3) phase were observed in a very narrow X range (0 < X < 0.02) prior to the vesicle phase.

Cryoelectron Microscopy↗
PubMed2006

One-dimensional assemblies of platinum nanoparticles on a graphite surface using nonionic/ionized mixed hemicylindrical micelle templates.

One-dimensional (1-D) self-assemblies of Pt nanoparticles on a graphite surface have been synthesized via a template-directed sintering process of individual nanoparticles, using nonionic/cationic mixed hemicylindrical micelle templates of dodecyldimethylamine oxide surfactant at graphite/solution interfaces. The dimension and morphology of Pt nanoparticles can be widely controlled by the concentration of Pt ions equivalent to the mixing ratio of nonionic and cationic species in the surfactant micelle. This approach could be extended to fabricate a wide range of self-assembling metallic nanostructures on surfaces using various nonionic/cationic mixed micelle-like self-assemblies carrying metal ions at interfaces, while providing a fundamental insight into a 1-D self-assembly from individual nanoparticles.

Journal Article↗
PubMed2006

Mode of interaction of amphiphilic alpha-helical peptide with phosphatidylcholines at the air-water interface.

Surface pressure (pi)-, surface potential (deltaV)-, and dipole moment (mu(perpendicular))-area (A) isotherms and morphological behavior were examined for monolayers of a newly designed 18-mer amphiphilic alpha-helical peptide (Hel 13-5), DPPC, and DPPC/egg-PC (1:1) and their combinations by the Wilhelmy method, ionizing electrode method, fluorescence microscopy (FM), and atomic force microscopy (AFM). The newly designed Hel 13-5 showed rapid adsorption into the air-liquid interface to form interfacial films such as a SP-B function. Regardless of the composition and constituents in their multicomponent system of DPPC/egg-PC, the collapse pressure (pi(c); approximately 42 mN m(-1)) was constant, implying that Hel 13-5 with the fluid composition of egg-PC is squeezed out of Hel 13-5/DPPC/egg-PC monolayers accompanying a two- to three-dimensional phase transformation. FM showed that adding a small amount of Hel 13-5 to DPPC induced a dispersed pattern of ordered domains with a "moth-eaten" appearance, whereas shrinkage of ordered domains in size occurred for the DPPC/egg-PC mixture with Hel 13-5. Furthermore, AFM indicated that (i) the intermediate phase was formed in pure Hel 13-5 systems between monolayer states and excluded nanoparticles, (ii) protrusions necessarily located on DPPC monolayers, and (iii) beyond the collapse pressure of Hel 13-5, Hel 13-5 was squeezed out of the system into the aqueous subphase. Furthermore, hysteresis curves of these systems nicely resemble those of the DPPC/SP-B and DPPC/SP-C mixtures reported before.

Adsorption↗
PubMed2006

Modification of gold nanorods using phosphatidylcholine to reduce cytotoxicity.

Hexadecyltrimethylammonium bromide (CTAB), which is necessary for the preparation of gold nanorods (NRs), was extracted from a NR solution into a chloroform phase containing phosphatidylcholine (PC). After three extractions, the zeta potential of the NRs remained positive, but its magnitude decreased from +67 +/- 1 to +15 +/- 1 mV. Transmission electron microscopy and energy-dispersive X-ray analysis indicated that the NRs were passivated with PC. The PC layer on the NR surface contributed to the prevention of NR aggregation. The PC-passivated NRs showed low cytotoxicity in comparison with twice-centrifuged NRs. It was shown that a negligible amount of CTAB was dispersed in the NR solution after the extraction. The extraction using a chloroform phase containing PC was found to be a convenient way of replacing the CTAB with alternative capping agents such as PC. This is a key technique for preparing functional NRs that can have practical applications.

Cell Survival↗
PubMed2005

Single-crystalline platinum nanosheets from nonionic surfactant 2-D self-assemblies at solid/aqueous solution interfaces.

Single-crystalline platinum nanosheets have been prepared via a new methodology based on the chemical reduction of a platinum salt (H2PtCl6) with hydrazine at a graphite/solution interface, using polyoxyethylene (20) sorbitan monostearate (Tween 60) based self-assembly (hemicylindrical micelle) templates. The platinum nanosheets with a uniform thickness of as thin as 3.5 +/- 1 nm are surface-smooth and continuous over relatively large length scales of micrometer sizes. In striking contrast to the Tween 60 based system, no Pt nanosheets are obtained with nonaethylene glycol monododecyl ether (C12EO9) and polyoxyethylene (23) dodecyl ether (C12EO23). No Pt nanosheets are also obtainable with a laterally homogeneous layer of Tween 60 formed at the silica/solution interface. These results indicate that surfactant Tween 60 molecules with a triple polyoxyethylene structure, as well as their hemicylindrical micelle templates, play an essential role for the formation of the Pt nanosheets. It is also suggested that the interfacially directed growth of Pt metals within the aqueous shells of the Tween 60 hemicylindrical micelles induces the thin Pt crystals as thick as the aqueous shells. The present approach could be extended to prepare a wide range of novel nanostructures of noble metals, using various micelle-like self-assemblies at interfaces.

Journal Article↗
PubMed2005

Effects of micelle-to-vesicle transitions on the degree of counterion binding.

Effects of micelle-to-vesicle transitions on the degree of counterion binding (beta) were investigated on three systems. For the concentration-dependent micelle-to-vesicle transition in the didodecyldimethylammonium bromide (DDAB)/water system, in the region of coexistent micelles and vesicles, less than 3 mM, the beta values increased significantly with DDAB concentration: beta (0.07 mM)=0.35 and beta (3 mM)=0.93. In the coexistent region, activities of the bromide ion, a(Br), were almost independent of the DDAB concentration, suggesting the pseudo-phase nature of both micelles and vesicles. In the concentration-dependent vesicle-to-lamellar transition region above 5 mM, where multilamellar vesicles were prevailing, on the other hand, the beta values were only little affected by this transition. This suggests that the increase in the layer number of DDAB multilamellar vesicles scarcely affects the beta values. This was also supported by the fact that the destruction of multilamellar vesicles by ultrasonication did not change the beta values. These results strongly suggest that the inner and outer monolayers of DDAB multilamellar vesicles are characterized by similar beta values. The second system, cetyltrimethylammonium bromide (CTAB)/DDAB mixtures, showed composition-dependent transitions depending on the mole fraction of DDAB X(DDAB): spherical micelles (0 rodlike micelles (0.2 vesicles (0.6<X(DDAB)<1). Values of beta increased with both the sphere-to-rodlike micelle transition and the micelle-to-vesicle transition. The increase in the beta value was larger for the latter than for the former transition. Little effects of ultrasonication on beta was also observed for the multilamellar vesicles of CTAB/DDAB mixtures. In the third system of the mixtures of two single chain surfactants, protonated and non-protonated of oleyldimethylamine oxide, the dependence of beta on the degree of ionization (alpha) can be well described with a theoretical curve, derived on the basis of the linear relation between the surface charge density and the alpha value, despite the occurrence of the micelle-to-vesicle transition.

Journal Article↗
PubMed2005

Protonation-induced structural change of lyotropic liquid crystals in oley- and alkyldimethylamine oxides/water systems.

Lyotropic phase behavior of the nonionic and the half-ionized oleyldimethylamine oxide (OlDMAO)/water systems was investigated using polarized light microscopy, small-angle X-ray diffraction, and differential scanning calorimetry. Nonionic OlDMAO formed isotropic micellar solution, nematic, hexagonal, cubic, and lamellar liquid crystalline phases as the surfactant concentration increased. In contrast, half-ionized OlDMAO (i.e., 1:1 mixture of the nonionic and the protonated species) had a greater tendency to form bilayer structures, and the phase diagram became quite similar to those of double-chained ionic surfactants rather than single-chained ones, despite the introduction of positive charges to the nonionic one. The preference of the bilayer structures in the half-ionized OlDMAO was interpreted in terms of the dimers stabilized by the hydrogen bond between the nonionic and protonated species. For alkyldimethylamine oxides with a saturated hydrocarbon chain (CnDMAO, chain length: n = 14, 16, and 18), the phase sequence of lyotropic liquid crystals was hardly affected by the protonation, but an elongation of the cylinders of the hexagonal phase was observed for the half-ionized C14DMAO. Consequently, it can be considered that the dominant bilayer formation of the half-ionized OlDMAO is attributed to the combined effect of the hydrogen-bonded dimer formation and the cis-double-bond configuration of the alkyl chain.

Journal Article↗
PubMed2005

Properties of two-component Langmuir monolayer of single chain perfluorinated carboxylic acids with dipalmitoylphosphatidylcholine (DPPC).

The surface pressure (pi)- and the surface potential (DeltaV)-area (A) isotherms were obtained for two-component monolayers of four different perfluorocarboxylic acids (FCns; perfluorododecanoic acid: FC12, perfluorotetradecanoic acid: FC14, perfluorohexadecanoic acid: FC16, perfluorooctadecanoic acid: FC18) with dipalmitoylphosphatidylcholine (DPPC) on substrate solution of 0.15 M NaCl (pH 2.0) at 298.2 K as a function of compositions in the mixtures by employing the Wilhelmy method, the ionizing electrode method, the fluorescence microscopy, and the atomic force microscopy. The data for the two-component monolayers on these systems were analyzed in terms of the additivity rule. Assuming a regular surface mixture, the Joos equation which allows one to describe the collapse pressure of a two-component monolayer with miscible components was used to declare the miscibility of the monolayer state, and an interaction parameter and an interaction energy were calculated. The new finding was that FCns and DPPC are miscible or immiscible depending on chain length increment of fluorocarbon part. That is, FC12/DPPC monolayer was perfectly miscible, and FC14/DPPC, and FC16/DPPC (0 < or = X(FC16) < or = 0.3) monolayers were partially miscible. While FC16/DPPC (0.3 < X(FC16) < 1) and FC18/DPPC systems are immiscible in the monolayer state. Furthermore, the mean molecular area, the surface dipole moment, and the phase diagrams enabled us to estimate the molecular orientation of four different perfluorocarboxylic acids/DPPC in the two-component monolayer state. One type of phase diagrams was obtained and classified into the positive azeotropic type. The miscibility of FCns and DPPC in the monolayer was also supported by fluorescence microscopy and atomic force microscopy. FC12/DPPC, FC14/DPPC and FC16/DPPC (0 < or = X(FC16) < or = 0.3) two-component monolayers on 0.15 M NaCl (pH 2) showed that FC12, FC14 and FC16 (0 < or = X(FC16) < or = 0.3) can dissolve or partially dissolve the ordered solid DPPC domains formed upon compression. This indicates that these fluorinated amphiphiles soften or harden the lipid depending on their chain length.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2005

Temperature-induced sedimentation to dispersion of ionic vesicles.

We present a temperature-induced sedimentation/dispersion transition of ionic vesicles in the system of alkyldimethylamine oxide hemihydrochloride (CnDMAO.1/2HCl) with a hydrocarbon chain length of 12-16 (n = 12, 14, and 16) and sodium 2-naphthalenesulfonate (NaNphS). The temperature-sensitive sedimentation/dispersion of ionic vesicles took place around a temperature of 50 degrees C, which was weakly dependent on the alkyl chain length. The combined effect of the thermally induced dissociation of the counterions from the vesicle and a hydrogen bonding between the nonionic and the cationic head groups is likely to be responsible for this unique behavior.

Chemical Precipitation↗
PubMed2005

Cytomegalovirus infection inhibits the expression of N-methyl-D-aspartate receptors in the developing mouse hippocampus and primary neuronal cultures.

Cytomegalovirus (CMV) is the most significant infectious cause of developmental brain disorders in humans. The infection occasionally persists and causes neurological disorders. The N-methyl-D-aspartate (NMDA) subtype of glutamate receptors is essential for the development and plasticity of synapses, but also is involved in neuronal excitotoxicity during viral infection. Here we investigated the effects of murine CMV (MCMV) infection on the expression of NMDA receptors in the hippocampal neurons of neonatal mice and primary neuronal cultures. Viral antigen was mostly found in hippocampal pyramidal neurons from the CA1 to CA3. Image analysis of immunohistochemistry demonstrated that the expression of NMDA receptor subunit 1 (NMDA-R1) protein in CA1 neurons of MCMV-infected brain was reduced to 40% of that in uninfected brain. The signal of in situ hybridization for NMDA-R1 mRNA was also decreased in CA1 neurons of MCMV-infected brain. In primary neuronal cultures, reduction of NMDA-R1 expression in MCMV-infected neurons was also detected by immunocytochemistry and Western blotting. These results suggest that reduction of NMDA receptor expression by MCMV infection may cause a decrease in the susceptibility of the neurons to excitotoxic cell death, and may be related to the establishment of viral persistence and functional disturbances in MCMV-infected neurons.

Animals↗
PubMed2005

Complex formation in alkyldimethylamine oxide/sodium palmitate/water mixtures.

The complex formation between nonionic alkyldimethylamine oxide (CnDMAO, n=14, 16, and 18) and sodium palmitate (NaPa) in the solid phase of CnDMAO/NaPa mixtures and the dependence of the interaction parameter beta of the regular solution theory (RST) on the mixed micelle composition of C16DMAO/NaPa mixtures were investigated. The dissolution temperature showed a maximum at a NaPa mole fraction X(Pa)(*) of 0.3-0.4 for C16DMAO/NaPa and 0.2 for C18DMAO/NaPa. The compositions of the complexes suggested by X(Pa)(*) are C16DMAO: NaPa=3:2 or 2:1 and C18DMAO:NaPa=4:1. The composition X(Pa)(*) depended on the chain length of the amine oxides. The maximum was not observed in the case of the C14DMAO/NaPa/water system. In the range 0.7< or =X(Pa)< or =1.0, dissolution temperature depression was observed with decreasing X(Pa). The dissolution temperature depression was analyzed by taking into account the nonideal behavior in the mixed micelles and the counterion binding on the mixed micelle surface. The negative beta values were obtained for all three mixed systems. It was shown that the counterion activity remained practically constant in the range of 0.7< or =X(Pa)< or =1.0. The cmc values of C16DMAO/NaPa mixtures were determined by pyrene fluorescence measurement. For C16DMAO/NaPa mixtures, the dependence of the RST interaction parameter beta on the mixed micelle composition X(Pa) was determined for a wide range (0.2< or =X(Pa) < or =0.9). In the range 0.2< or =X(Pa)< or =0.5, the beta values were obtained from an analysis of cmc based on the RST. In the range 0.7< or=X(Pa)< or=0.9, the beta values were obtained from an analysis of the dissolution temperature depression. From the analysis of the micelle composition dependence of the beta values, a short-range attractive interaction between the headgroup of C16DMAO and palmitate anion is suggested.

Journal Article↗
PubMed2004

Micelle-vesicle transition of oleyldimethylamine oxide in water.

We studied the effects of the degree of ionization(alpha) and the surfactant concentration (C(d)) on the micelle-vesicle transition in salt-free oleyldimethylamine oxide (OlDMAO) aqueous solutions by the dynamic light scattering (DLS), the hydrogen ion titration, the small angle neutron scattering (SANS), the electrophoretic light scattering (ELS) and viscoelastic measurements. From the study of ionization effects, the micelle-vesicle transition was recognized as a change of aggregate size by the DLS measurement; however, the micelle-vesicle transition was not detected both in the ELS measurement and the hydrogen ion titration, suggesting that the electric properties of the worm-like micelles and the vesicles are very similar despite a large difference of shapes between them. From the results of the SANS, the DLS and the viscosity measurements, it was suggested that a concentration-dependent micelle-vesicle transition took place around C(p)=10 mmolkg-1 for the solutions at alpha=0.5. In the concentration-range 10 mmolkg-1<C(d)<150 mmolkg-1, the micelles and the vesicles coexisted. In the concentration region (C(d) = 10-50 mmolkg-1), the vesicle size increased with the surfactant concentration.

Electrophoresis↗
PubMed2003

Neuron-specific activation of murine cytomegalovirus early gene e1 promoter in transgenic mice.

The brain is the main target in congenital cytomegalovirus (CMV) infection and immunocompromised patients. No definite evidence that a CMV has special affinity for the central nervous system (CNS) has been published. Here, we generated transgenic mice with an e1 promoter/enhancer region connected to the reporter gene lacZ. Surprisingly, expression of the transgene was completely restricted to the CNS in all lines of transgenic mice. The transgene was expressed in subpopulation of neurons in the cerebral cortex, hippocampus, diencephalon, brainstem, cerebellum, and spinal cord in all of the lines. Non-neuronal cells in the CNS were negative for transgene expression. Activation of the transgene was first observed in neurons of mesencephalon in late gestation, and then the number of positive neurons increased in various parts of the brain as development proceeded. Upon infection of the transgenic mouse brains with MCMV, the location of the activated neurons became more extensive, and the number of such neurons increased. These results suggest that there are host factor(s) that directly activate the MCMV early gene promoter in neurons. This neuron-specific activation may be associated with persistent infection in the brain and may be responsible for the neuronal dysfunction and neuronal cell loss caused by CMV infection.

Animals↗
PubMed2003

Brain slice culture for analysis of developmental brain disorders with special reference to congenital cytomegalovirus infection.

Cytomegalovirus (CMV) is the most significant infectious cause of congenital abnormalities of the central nervous system (CNS) with variation from the fatal cytomegalic inclusion disease to functional brain disorder. The phenotype and degree of the brain disorder depends on infection time during the developing stage, virulence, route of infection and the viral susceptibility of the cells. The pathogenesis of the CMV infection to the CNS seems to be strongly related to neural migration, neural death, cellular compositions and the immune system of the brain. To understand the complex mechanism of this disorder, we used organotypic brain slice cultures. In the brain slice culture system, migration of CMV-infected neuronal cells was observed, which reflects infectious dynamics in vivo. Neural progenitor cells or glial immature cells in the subventricular zone and marginal area are most susceptible to murine cytomegalovirus (MCMV) infection in this system. The susceptibility declined as the number of immature glial cells decreased with age. The immature glial cells proliferated in brain slice cultures during prolonged incubation, and the susceptibility to MCMV infection also increased in association with the proliferation of these cells. The brain slice from an immunocompromised mouse (Beige-SCID mouse) unexpectedly showed lower susceptibility than that of an immunocompetent mouse during any prolonged incubation. These results suggest that the number of immature glial cells might determine the susceptibility of CMV infection to the brain, independent of the immune system. We reviewed recent findings of CMV infection to the brain from the perspective of brain slice cultures and the possibility that this system could be a useful method to investigate mechanisms of congenital anomaly of the brain.

Animals↗