Biomedical subjects

Yoshihiro Fukui

Publications and source records attributed to Yoshihiro Fukui.

11 recordsLinked to original sources

PubMed2003

A genetic mouse model carrying the nonfunctional xeroderma pigmentosum group G gene.

A genetic mouse model with a disrupted XPG allele was generated by insertion of neo cassette sequences into exon 3 of the XPG gene by using embryonic stem (ES) cell techniques. The xpg-deficient mice showed distinct developmental characteristics. Their body was marked smaller than that in wild-type littermates since the postnatal day 6, and this postnatal growth failure became more severe with developmental proceeding. Their life span was very short, all of the mutants died by postnatal day 23 after showing great weakness and emaciation. In addition, the mutant homozygous mice also showed some progressive neurological signs, like the lower level of activity and a progressive ataxia. Further examination indicated there was developmental retardation of the brain in the mutant mice. Their brain weight, and thickness of cerebral cortex and cerebellar cortex were significant different from the controls. These characteristics, like small size brain, brain developmental retardation and progressive neurological dysfunctions in the homozygotes were similar to the typical clinical phenotype of the XPG patients and Cockayne syndrome, we believe that the xpgdeficient mice will be an animal model for studying the function of the XP-G protein in nucleotide-excision repair and mechanisms related to the clinic symptoms of XP-G and Cockayne syndrome in humans.

Animals↗

PubMed2003

Expression of neural cell adhesion molecule L1 in the brain of rats exposed to X-irradiation in utero.

To gain insight to the cellular and molecular mechanisms involved abnormal neuronal migration induced by irradiation, we investigated expression of neuronal cell adhesion molecule L1 and neuronal migration in the brains through comparison between rats prenatally exposed to X-ray and controls. To observe the pattern of neuronal migration, bromodeoxyuridine (BrdU) was chosen as a marker to label migrating cells. The results showed some of the labeled cells remained in the lower of the cortical plate in the irradiated rats, suggesting that neuronal migration was disrupted by X-ray. To study change of expressing neural cell molecule L1, rat brains were analyzed by SDS-PAGE after isolation of L1 by immunoaffinity chromatography. In the all brain membrane fraction, immunoaffinity purified L1 had bands at 200, 180, 140 and 80 kDa. However, the bands in the irradiated group were very weak when compared with the control. Taking these results into account, abnormal neuronal migration and reduction of expression L1 found in the irradiated brain indicated that migration of neural cells may be largely dependent on radial glial fiber as well as neural cell molecules like L1. A decrease in L1 expression may be one of reasons of abnormal neuronal migration.

Animals↗

PubMed2002

Expression of inorganic phosphate/vesicular glutamate transporters (BNPI/VGLUT1 and DNPI/VGLUT2) in the cerebellum and precerebellar nuclei of the rat.

Expression of inorganic phosphate/vesicular glutamate transporters (BNPI/VGLUT1 and DNPI/VGLUT2) was studied in the cerebellum and precerebellar nuclei of rats using immunohistochemistry and in situ hybridization. DNPI/VGLUT2-stained mossy fibers were principally seen in the vermis (lobules I and VIII-X) and flocculus, whereas BNPI/VGLUT1-stained mossy fibers were localized throughout the cortex. Some vermal and floccular mossy fibers were stained for both transporters. High levels of DNPI/VGLUT2 mRNA hybridization signals were demonstrated in many neurons throughout the vestibular nuclear complex as well as the lateral reticular, external cuneate, inferior olivary and deep cerebellar nuclei. Significant BNPI/VGLUT1 mRNA signals were demonstrated in the lateral reticular nucleus and vestibular nuclear complex but not in the inferior olivary nucleus, indicating that climbing fibers have DNPI/VGLUT2 only. These results show that DNPI/VGLUT2 is expressed preferentially to vestibulo-, reticulo- and cuneocerebellar neurons, some of which also possess BNPI/VGLUT1, suggesting some differential and co-operative functions between DNPI/VGLUT2 and BNPI/VGLUT1 in the cerebellum.

Animals↗

PubMed2002

Differential expression of two distinct vesicular glutamate transporters in the rat retina.

Expression and cellular localization of vesicular glutamate transporters (BNPI and DNPI) were studied in the rat retina. RT-PCR showed expression of both transporter mRNAs. hybridization demonstrated BNPI mRNA signals in the inner segments of photoreceptors and the inner nuclear layer, whereas DNPI mRNA signals were confined to the ganglion cell layer. Punctate BNPI immunoreactivity was localized in the inner and outer plexiform layers, and weak DNPI immunoreactivity was detectable only in some cells and fibers of the ganglion cell layer. The present study suggests that BNPI exists in photoreceptors and bipolar cells, while DNPI is present in ganglion cells, as specific systems in distinct glutamatergic neurons of the retina.

Animals↗

PubMed2002

Adverse effects of maternal ethanol consumption on development of dorsal hippocampus in rat offspring.

We examined the laminar structure and distribution of mossy fiber terminal fields in the dorsal hippocampus, an important area for spatial learning, in rats exposed to ethanol during gestational days 10-21. Pyramidal cells in the CA3a subfield were loosely packed compared to control rats. Aberrant infra- and intrapyramidal mossy fibers were found in the CA3 region, especially in the CA3a subfield, throughout the dorsal hippocampus of ethanol-exposed rats. Aberrant mossy fiber terminals were observed more frequently in the rostral than the caudal level of the dorsal hippocampus. At the most caudal level of the dorsal hippocampus, disarrangement of pyramidal cells was seen in the CA3c subfield along with disturbed mossy fiber terminals. Immunohistochemical studies revealed that neural cell adhesion molecule (NCAM) was not related to aberrant distribution of mossy fiber terminals after prenatal exposure to ethanol. Parvalbumin immunoreactivity was increased in the dorsal hippocampus of ethanol-exposed rats compared with control rats. Abnormal development of the dorsal hippocampus induced by prenatal ethanol exposure may be associated with the defect of spatial memory seen in fetal alcohol syndrome children and their animal models.

Alcohol Drinking↗

PubMed2002

Administration schedule for an ethanol-containing diet in pregnancy affects types of offspring brain malformations.

In the present study, we administered liquid diets containing ethanol to pregnant rats on different schedules, and examined the cerebral cortex of their pups on gestational day (GD) 21 by immunohistochemistry. The first group of pregnant rats was fed a liquid diet containing 5% (w/v) ethanol during GDs 10-21(5% Et). The second group was fed a liquid diet containing 2.5% (w/v) ethanol on GDs 10-12, a diet containing 4% (w/v) ethanol on GDs 13-15, and a diet containing 5% (w/v) ethanol on GDs 16-21 (2.5-5% Et). Pups of 5% Et dams had leptomeningeal heterotopias mainly in the parietal cortex. In 2.5-5% Et pups, other types of malformations such as grooves, microgyri, stacked-up cortices, and defects of layer I were found. The diet intake and body weight gain of 2.5-5% Et dams were significantly higher than those of 5% Et dams during GDs 11-16. There was no difference in total ethanol consumption during GDs 10-21 between the two groups. However, ethanol consumption on GD 15 in 2.5% Et was higher than in 5% Et. A different schedule for administration of an ethanol-containing diet in pregnancy might induce different types of cerebral malformations in rat fetuses.

Alcohol-Induced Disorders, Nervous System↗

PubMed2002

A selective loss of small-diameter myelinated optic nerve axons in rats prenatally exposed to ethanol.

Pregnant rats were fed an ethanol-containing liquid diet between gestational days 10 and 21. The optic nerves of their litters at 49 days of age were examined using quantitative stereological procedures. Cross-sectional areas of the optic nerve in ethanol-exposed rats were significantly smaller than those in controls. This was reflected in the reduced number of myelinated fibers, but not of non-myelinated fibers. The size distribution histogram indicated a decreased number of small axonal-diameter myelinated fibers in ethanol-exposed rats. The results suggested optic nerve hypoplasia in ethanol-exposed rats characterized by a selective loss of small-diameter myelinated fibers.

Animals↗

PubMed2002

Types and three-dimensional distribution of neuronal ectopias in the brain of mice prenatally subjected to X-irradiation.

The types and three-dimensional distribution of neocortical ectopias following prenatal exposure to X-irradiation were studied by a histological examination and computer reconstruction techniques. Pregnant ICR mice were subjected to X-irradiation at a dose of 1.5 Gy on embryonic day 13. The brains from 30-day-old mice were serially sectioned on the frontal plane at 15 microns, stained with HE and observed with a microscope. The image data for the sections were input to a computer, and then reconstructed to three-dimensional brain structures using the Magellan 3.6 program. Sectional images were then drawn on a computer display at 240 microns intervals, and the positions of the different types of neocortical ectopias were marked using color coding. Three types of neocortical ectopias were recognized in the irradiated brains. Neocortical Lay I ectopias were identified as small patches in the caudal occipital cortex, and were located more laterally in the neocortex in caudal sections than in the rostral sections. Periventricular ectopias were located more rostrally than Lay I ectopias, and were found from the most caudal extent of the presumed motor cortex to the most caudal extent of the lateral ventricle. Hippocampal ectopias appeared as continuous linear bands, and were frequently associated with the anterior parts of the periventricular ectopias.

Animals↗

PubMed2002

Distribution of calbindin-D28K immunoreactive neurons in rat primary motor cortex.

Distribution of calbindin-D28K immunoreactive cells in the primary motor area of the adult rat neocortex was studied in the present experiment. In the primary motor cortex, calbindin-D28K immunoreactivity was found in two populations of cortical neurons. One was composed of neurons heavily labeled with anti-calbindin antibody, which were present in two bands corresponding to cortical layers II-III, and V. The morphological types of these cells were varied; they had oval, fusiform or mutiangular somata. The proximal dendrites of the heavily stained cells showed that these cells were non-pyramidal neurons, and they were either bitufted or multipolar cells. The other was a weakly stained population, mainly concentrated in layers II and III, that also contained pyramidal neurons. In addition, one outstanding feature of the neuropil staining deep to layer II was the labeling of the long, vertically oriented bundles of immunoreactive processes. Such a distinct pattern of calbindin-D28K immunoreactive neurons in the primary motor cortex suggests a relatively high density of calcium channels exists in the superficial layers of the rat primary motor cortex.

Animals↗

PubMed2002

Normal and abnormal neuronal migration in the developing cerebral cortex.

Neuronal migration is the critical cellular process which initiates histogenesis of cerebral cortex. Migration involves a series of complex cell interactions and transformation. After completing their final mitosis, neurons migrate from the ventricular zone into the cortical plate, and then establish neuronal lamina and settle onto the outermost layer, forming an "inside-out" gradient of maturation. This process is guided by radial glial fibers, requires proper receptors, ligands, other unknown extracellular factors, and local signaling to stop neuronal migration. This process is also highly sensitive to various physical, chemical and biological agents as well as to genetic mutations. Any disturbance of the normal process may result in neuronal migration disorder. Such neuronal migration disorder is believed as major cause of both gross brain malformation and more special cerebral structural and functional abnormalities in experimental animals and in humans. An increasing number of instructive studies on experimental models and several genetic model systems of neuronal migration disorder have established the foundation of cortex formation and provided deeper insights into the genetic and molecular mechanisms underlying normal and abnormal neuronal migration.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2002

Immunohistochemistry of voltage-gated calcium channel alpha1B subunit in mouse cerebellum.

Secretion of neurotransmitters is initiated by voltage-gated calcium influx through presynaptic, voltage- gated N-type calcium channels. However, little is known about their cellular distribution in the mouse cerebellum. In the cerebellum, alpha1B immunoreactivity is found mainly on the cell bodies of all Purkinje cells. In addition, the immunoreactivity was detected on a subset of Purkinje cell dendrites, clustered to form a parasagittal array of bands. In the anterior lobe vermis, immunoreactive Purkinje cell dendrites form narrow stripes separated by broad bands of unstained dendrites. Moving caudally through the vermis, these stripes become thicker as a larger fraction of the Purkinje cell dendrites become immunoreactive. This localization study of the alpha1B pore-forming subunits in mouse cerebellum may guide future investigations of the role of calcium channels in neurological pathways.

Animals↗