Yoshihiro Fukui

The University of Tokushima, Tokusima, Tokushima, Japan

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Publications (118)273.22 Total impact

  • Ken-ichi Ohta · Hiromi Sakata-Haga · Yoshihiro Fukui ·
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    ABSTRACT: Previous studies have suggested that ethanol exposure during brain development affects responses to fear and anxiety after maturity. To clarify in detail the impaired behavior related to fear and anxiety seen in rat offspring prenatally exposed to ethanol, their behaviors were observed using an elevated T-maze (ETM) test, which allows assessment of passive avoidance acquisition and one-way escape separately, and an elevated open platform (EOP) test for the assessment of unconditioned freezing against innate fear. The ETM test revealed that acquisition of passive avoidance was significantly inhibited in prenatally ethanol-exposed rats, while their escape behavior was not altered. In the EOP test, the duration of the freezing behavior was significantly elongated in prenatally ethanol-exposed offspring. Thus, we concluded that prenatal ethanol exposure could impair acquisition of passive avoidance, while it could facilitate a response related to unconditioned fears in rat offspring.
    Behavioural brain research 07/2012; 234(2):255-8. DOI:10.1016/j.bbr.2012.07.001 · 3.03 Impact Factor
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    ABSTRACT: Our article summarizes a series of studies about fetal gyrification and its relation to cerebral growth in cynomolgus monkeys. Based on the cerebral growth (i.e., brain weight, cerebral volume, and frontooccipital length of the cerebral hemisphere) and the developmental pattern of gyrification in each sulcus of cynomolgus monkeys, we divided the gyrification process into four stages: Stage 1. Demarcation of cerebral lobes and limbic gyri; Stage 2. Demarcation of neocortical gyri; Stage 3. Emergence of secondary and tertiary sulci; and Stage 4. Growth of sulcal length and depth. Each stage of those gyrification processes was influenced by different developmental events, such as the emergence of corticocortical long-associative fiber tracts, cortical maturations, and subcortical white-matter development. This is the first report to systematically propose gyrification processes closely related to the order of phyologenetical development of the cerebral cortex in primates.
    The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 07/2012; 295(7):1065-74. DOI:10.1002/ar.22478 · 1.54 Impact Factor
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    Kazuhiko Sawada · Yoshihiro Fukui ·
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    ABSTRACT: Tottering mouse is an ataxic mutant that carries a mutation in a gene encoding for the 1A subunit of P/Q-type Ca 2+ channel (Ca v 2.1), and exhibits Purkinje cells loss with the zebrin II immunonegative population in the anterior vermis and the zebrin II immunopositive popula-tion in the caudal vermis. This study aimed to clarify relationship between patterns of Pur-kinje cell loss in the tottering cerebellum with expression of non-phosphorylated forms of the neurofilament heavy chain (NFH), which was recognized by ani-SMI-32. SMI-32 immu-nostaining has appeared in particular subsets of Purkinje cells, which were organized into parasagittal stripes throughout the cerebellar cortex of control mice. In tottering mice, SMI-32 stripes in the vermis disappeared from the a selective loss of SMI-32 immunopositive Purkinje cells. When the phosphorylation state of NFH was examined immunohistochemi-cally using anti-SMI-31, which recognizes phosphorylation epitopes of NFH, no Purkinje cell soma were labeled in either tottering or control mice. In addition, while a number of Purkinje cell axonal torpedoes were observed in tottering mice but not in control mice, all torpedoes were stained with both anti-SMI-32 and anti-SMI-31, revealing the presence of both phos-phorylated and non-phosphoryalted forms of NFH in the torpedoes. These results predict that the non-phosphorylated form of NFH expressing cerebellar Purkinje cells is susceptible to the Ca v 2.1 gene defect to degenerate those neurons. This may result in the characteristic parasagittal pattern of Purkinje cell loss in tottering mice.
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    ABSTRACT: Cynomolgus monkey (Macaca fascicularis) is a popular laboratory primate belonging to Old World monkeys, which are the group most closely related to humans except for the apes. This paper summarizes a series of our studies regarding the development of cerebral sulci and gyri in this primate, and the stated possibility of evaluation of the sulcal development for assessing the developmental toxicity testing. The cerebrum of cynomolgus monkeys experienced a regular sequence of emergence of sulci and gyri on gross observation while such timetables corresponded to those obtained by magnetic resonance imaging (MRI) with a lag time of 10-30 days. When the timetables for the emergence of anatomically identical primary sulci and gyri were compared between cynomolgus monkeys and humans, their chronological sequences were comparable, while some sulci and gyri located on the phylogenetically newer cortical region in humans emerged earlier in monkeys. The present paper further indicates brief procedures for evaluating cerebral abnormalities and/or maturity using brain specimens without MRI measurements. The primary sulcal lengths measured by the 'cotton thread' method were a brief index of the degree of regional gyrification. As the development of a calcarine sulcus was closely correlated with morphological maturation of the lateral ventricle, which changed drastically during embryonic days (EDs) 90-100, the cerebral maturity on ED 100 could be evaluated by the infolding of that sulcus. Thus, the present paper provides gross anatomical and MRI references and brief procedures for investigating the normality of the development of cerebral sulci and gyri of laboratory primates, cynomolgus monkeys.
    Congenital Anomalies 03/2012; 52(1):16-27. DOI:10.1111/j.1741-4520.2011.00352.x · 1.08 Impact Factor
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    ABSTRACT: The present study aimed to quantitatively clarify the gross anatomical asymmetry and sexual dimorphism of the cerebral hemispheres of cynomolgus monkeys. While the fronto-occipital length of the right and left cerebral hemispheres was not different between sexes, a statistically significant rightward asymmetry was detected in the cerebral width at the perisylvian region in females, but not in males (narrower width of the left side in the females). An asymmetry quotient of the sulcal lengths revealed a rightward asymmetry in the inferior occipital sulcus and a leftward asymmetry in the central and intraparietal sulci in both sexes. However, the laterality of the lengths of other sulci was different for males and females. The arcuate sulcus was directed rightward in males but there was no rightward bias in females. Interestingly, the principle sulcus and lateral fissure were left-lateralized in the males, but right-lateralized in the females. The results suggest that lateralization patterns are regionally and sexually different in the cerebrum of cynomolgus monkeys. The present results provide a reference for quantitatively evaluating the normality of the cerebral cortical morphology in cynomolgus monkeys.
    Congenital Anomalies 12/2011; 51(4):161-6. DOI:10.1111/j.1741-4520.2011.00330.x · 1.08 Impact Factor
  • Shiro Tochitani · Shigeaki Kondo · Hiromi Sakata-Haga · Yoshihiro Fukui ·

    Neuroscience Research 09/2011; 71. DOI:10.1016/j.neures.2011.07.532 · 1.94 Impact Factor

  • Neuroscience Research 09/2011; 71. DOI:10.1016/j.neures.2011.07.528 · 1.94 Impact Factor
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    ABSTRACT: In the present study developmental changes in the cerebral sulci and volumes of subcortical and archicortical structures of the cerebrum in cynomolgus monkey fetuses were examined with T(1)-weighted magnetic resonance (MR) images in 3D. On the embryonic day (ED) 90, the lateral ventricle had still an immature vesicular shape in the occipital region of the cerebrum, and it dramatically closed its lumen by ED 100. In that period the calcarine sulcus progressively infolded from the medial surface of the cerebral hemisphere narrowing the lumen of the lateral ventricle in the occipital region. Volume of the lateral ventricle decreased in the period ED 90-100, increasing afterwards in spite of increasing volumes of subcortical and archicortical structures such as the caudate nucleus, putamen, globus pallidus, amygdala and hippocampal formation. During the same time, the volume of the germinal matrix around lateral ventricles decreased to disappear completely by ED 120. These results suggest that the morphological maturation of lateral ventricle is linked to the development of calcarine sulcus in cynomolgus monkey fetuses. The degree of infolding of calcarine sulcus on ED 100 would be useful as a gross anatomical landmark for evaluating the cerebral maturation in cynomolgus monkey fetuses.
    Acta neurobiologiae experimentalis 01/2011; 71(3):381-6. · 1.29 Impact Factor
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    Kazuhiko Sawada · Yoshihiro Fukui ·
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    ABSTRACT: The present study examined the development of the axonal torpedoes of the cerebellar Pur-kinje cells in a Ca v 2.1 channel mutant, rolling mouse Nagoya. Calbindin D-28k immunostain-ing revealed a few torpedoes in both the cerebellar white matter and all three subdivisions of the deep cerebellar nuclei of rolling mice on postnatal day (PD) 21, while there was no differ-ence in either number among the age-matched controls. On PD 120, the number of torpedoes drastically increased in the white matter of rolling mice. Their numbers in the deep cerebel-lar nuclei also increased in rolling mice during PDs 21 to 120 with no change in their distri-butions. These results suggest that the axonal torpedoes develop progressively with aging in non-specific populations of Purkinje cells in the rolling mouse cerebellum.

  • Neuroscience Research 12/2010; 68:e130-e131. DOI:10.1016/j.neures.2010.07.2148 · 1.94 Impact Factor
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    Kazuhiko Sawada · Yoshihiro Fukui ·
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    ABSTRACT: Rolling mouse Nagoya is an ataxic mutant mouse that carries a mutation in a gene encoding for the alpha 1A subunit of the voltage-gated P/Q-type Ca2+ channel (Cav2.1). This report summarizes our studies and others concerning cerebellar abnormalities in rolling mice based on chemical neuroanatomy. While there are no obvious cerebellar deformations in this mutant mouse, the altered functions of Purkinje cells can be revealed as a reduced expression of type 1 ryanodine receptor (RyR1) in all Purkinje cells uniformly throughout the cerebellum, and as an ectopic expression of tyrosine hydroxylase (TH) in the Purkinje cell subsets with the zebrin II-immunopositive phenotype. As the mutated Cav2.1 channel is expressed at uniform levels in all Purkinje cells, its copresence with RyR1 staining suggests that a Cav2.1 channel dysfunction links with the expression of RyR1 in Purkinje cells of rolling mice. However, an ectopic expression of TH in the Purkinje cells is topologically related to the projection of corticotrophin-releasing factor-immunopositive climbing fibers rather than expression of the mutated Cav2.1 channel. On the other hand, increased levels of serotonin (5-HT) in 5-HTergic fibers were revealed immunohistochemically in Purkinje cells of the vermis of rolling cerebellum. Thus, to determine whether or not cerebellar abnormalities are related to Purkinje cell populations revealed by zebrin II expression is essential for enhancing our understanding of the pathogenesis of hereditary cerebellar ataxic mutants such as rolling mice.
    The Scientific World Journal 10/2010; 10:2032-8. DOI:10.1100/tsw.2010.205 · 1.73 Impact Factor
  • Kazuhiko Sawada · Hiromi Sakata-Haga · Yoshihiro Fukui ·
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    ABSTRACT: The present study examined the spatial organization of tyrosine hydroxylase (TH) immunopositive Purkinje cells in the cerebellum of rolling mouse Nagoya with reference to the distribution pattern of the cerebellar compartmentation antigen, heat shock protein 25 (HSP25). Whole-mount immunostaining revealed a striking pattern of parasagittal stripes of TH staining in the rolling mouse cerebellum but not in the control cerebellum. Although the TH stripes resembled the zebrin II stripes in the rolling cerebellum, these two distributions did not completely overlap. The TH stripes were present in the lobules VI and VII (central zone), the lobule X (nodular zone), and the paraflocculus, where zebrin II immunostaining was uniformly expressed. Double immunostaining revealed that TH stripes were aligned in an alternative fashion with HSP25 stripes within the caudal half of lobule VIb, lobules IXb and X, and paraflocculus. Some, but not all, TH stripes shared boundaries with HSP25 stripes. These results revealed an alternating array of TH immunopositive Purkinje cell subsets with HSP25 immunopositive Purkinje cells in the zebrin II-defined transverse zone of the rolling mouse cerebellum. The constitutive expression of HSP25 may prevent the ectopic expression of TH in zebrin II immunopositive Purkinje cell subsets.
    Brain research 05/2010; 1343:46-53. DOI:10.1016/j.brainres.2010.04.062 · 2.84 Impact Factor
  • Shiro Tochitani · Hiromi Sakata-Haga · Yoshihiro Fukui ·
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    ABSTRACT: Neural progenitors in the ventricular zone of the developing neocortex divide oriented either parallel or perpendicular to the ventricular surface based on their mitotic spindle orientation. It has been shown that the cleavage plane orientation is developmentally regulated and plays a crucial role in cell fate determination of neural progenitors or the maintenance of the proliferative ventricular zone during neocortical development. We tested if fetal exposure to ethanol, the most widely used psychoactive agent and a potent teratogen that may cause malformation in the central nervous system, alters mitotic cleavage orientation of the neural progenitors at the apical surface of the ventricular zone in the developing neocortex. Fetal exposure to ethanol on E10.5 and 11.5 increased the occurrence frequency of a horizontal cleavage plane that is parallel to the ventricular surface on E 12.5. Administration of picrotoxin, a GABA(A) receptor antagonist, prior to ethanol administration canceled the effect of ethanol with the frequency of horizontal division similar to the control level, although picrotoxin itself did not show any effect on cleavage plane orientation. Phenobarbital, a GABA(A) receptor agonist, induced horizontal cleavage to an extent similar to that induced by ethanol administration. (+)MK801, an antagonist of NMDA receptor that is another major target of ethanol in neural cells, did not affect the cleavage plane of dividing progenitors. These results suggest that fetal ethanol exposure induced alterations in the cleavage plane orientation of neural progenitors in the ventricular zone of the neocortex via the enhancement of the function of GABA(A) receptors.
    Neuroscience Letters 02/2010; 472(2):128-32. DOI:10.1016/j.neulet.2010.01.071 · 2.03 Impact Factor
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    ABSTRACT: The ontogenetic pattern of gyrification and its relationship with cerebral cortical volume were examined in cynomolgus monkey fetuses. T(1)-weighted coronal magnetic resonance (MR) images at 7 T were acquired from the fixed cerebra of three male fetuses, each at embryonic days (EDs) 70 to 150, and the gyrification index (GI) of each slice was estimated. The mean GI was low (1.1-1.2) during EDs 70 to 90, and then increased dramatically on ED 100. The developmental profiles of the rostrocaudal GI distribution revealed that cortical convolution was more frequent in the parietooccipital region than in other regions during EDs 100 to 150, forming an adult-like pattern by ED 150. The mean GI was closely correlated with the volume of cortical gray matter (r=0.9877), and also with the volume of white matter/intermediate zone (r=0.8961). These findings suggest that cortical convolution is correlated with either the maturation of cortical gray matter or the development of white matter bundles. The characteristic GI distribution pattern of catarrhines was formed by ED 150 in correlation with the progressive sulcal infolding in the parietooccipital region of the cerebrum.
    Neuroscience 02/2010; 167(3):735-40. DOI:10.1016/j.neuroscience.2010.02.045 · 3.36 Impact Factor
  • Ken-ichi Ohta · Hiromi Sakata-Haga · Yoshihiro Fukui ·
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    ABSTRACT: It is known that the developing serotonergic system is one of the targets of ethanol teratogenicity. Because serotonin has multiple functions in both mature and immature brains, disturbance of the serotonergic system by ethanol exposure in utero can be cause of a wide range of psychiatric problems in adulthood. In the present study, we observed serotonergic neurons in the midbrain raphe nuclei and anxiety-like behaviors which would be affected by an altered serotonergic system in adult rats prenatally exposed to ethanol. Pregnant rats were fed a liquid diet containing 2.5-5.0% (w/v) ethanol on gestational days 10-21. Their offspring were examined at 60-70 days of age. A significant decrease in the number of serotonergic cells in the midbrain raphe nuclei was shown in prenatally ethanol-exposed offspring. In an open field test, they spent more time in a central area compared to controls. Also in an elevated plus maze test, prenatally ethanol-exposed offspring spent more time on the open arms than controls. These behavioral results suggested that prenatally ethanol-exposed rats were less sensitive to anxiety. However, 44% of prenatally ethanol-exposed offspring exhibited freezing behavior on the open arms of the elevated plus maze, causing strong anxiety, compared with 0% in intact control and 12.5% in isocaloric sucrose-fed control groups. These findings suggest that prenatal ethanol exposure decreases both susceptibility and resistance of anxiety. Insufficient serotonergic actions caused by reduced serotonergic neurons in the raphe nuclei might contribute to the alterations in anxiety-related behaviors observed in our prenatally ethanol-exposed rats.
    Congenital Anomalies 02/2010; 50(2):105-14. DOI:10.1111/j.1741-4520.2010.00269.x · 1.08 Impact Factor
  • Hiromi Sakata-Haga · Kenichi Ohta · Yoshihiro Fukui ·

    Neuroscience Research 12/2009; 65. DOI:10.1016/j.neures.2009.09.1281 · 1.94 Impact Factor

  • Neuroscience Research 12/2009; 65. DOI:10.1016/j.neures.2009.09.774 · 1.94 Impact Factor
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    ABSTRACT: The aim of this study was to spatio-temporally clarify gross structural changes in the forebrain of cynomolgus monkey fetuses using 7-tesla magnetic resonance imaging (MRI). T(1)-weighted coronal, horizontal, and sagittal MR slices of fixed left cerebral hemispheres were obtained from one male fetus at embryonic days (EDs) 70-150. The timetable for fetal sulcation by MRI was in good agreement with that by gross observations, with a lag time of 10-30 days. A difference in detectability of some sulci seemed to be associated with the length, depth, width, and location of the sulci. Furthermore, MRI clarified the embryonic days of the emergence of the callosal (ED 70) and circular (ED 90) sulci, which remained unpredictable under gross observations. Also made visible by the present MRI were subcortical structures of the forebrain such as the caudate nucleus, globus pallidus, putamen, major subdivisions of the thalamus, and hippocampal formation. Their adult-like features were formed by ED 100, corresponding to the onset of a signal enhancement in the gray matter, which reflects neuronal maturation. The results reveal a highly reproducible level of gross structural changes in the forebrain using a high spatial 7-tesla MRI. The present MRI study clarified some changes that are difficult to demonstrate nondestructively using only gross observations, for example, the development of cerebral sulci located on the deep portions of the cortex, as well as cortical and subcortical neuronal maturation.
    Brain Structure and Function 03/2009; 213(4-5):469-80. DOI:10.1007/s00429-009-0204-x · 5.62 Impact Factor
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    ABSTRACT: In the present study, we examined by immunohistochemistry the formation and distribution of 8-nitroguanine, a sensitive marker of nitrosative DNA damage, in rat stomach of rats subjected to water immersion restraint stress (WIR). WIR induced an increase in 8-nitroguanine content of gastric gland epithelium. 8-Nitroguanine immunoreactivity, which was observed mainly in the nuclei of stomach epithelium, increased with the severity of inflammation. Expression of iNOS was also observed in the inflammatory cells of lamina propria. Therefore, it is logical that iNOS-mediated nitrosative stress must participate in the development of ulcers through apoptotic cell death linked to the formation of 8-nitroguanine during chronic inflammation. Taurine administration attenuated stress-induced gastric mucosal injury. These results demonstrate that nitrosative stress participates in stress-mediated ulcer formation. Taurine exerts a prophylactic effect against mucosal lesions of the stomach caused by stress. This effect of taurine may have a potential clinical benefit in preventing gastritis associated with stress.
    Advances in Experimental Medicine and Biology 02/2009; 643:273-83. DOI:10.1007/978-0-387-75681-3_28 · 1.96 Impact Factor

Publication Stats

2k Citations
273.22 Total Impact Points


  • 1993-2012
    • The University of Tokushima
      • • Department of Anatomy and Developmental Neurobiology
      • • School of Medicine
      Tokusima, Tokushima, Japan
  • 1987-2008
    • Nagoya University
      • Research Institute of Environmental Medicine
      Nagoya, Aichi, Japan
  • 2007
    • Osaka Bioscience Institute
      Ōsaka, Ōsaka, Japan
  • 2002
    • National Institute of Radiological Sciences
      • Molecular Imagining Center
      Tiba, Chiba, Japan
    • Konyang University
      • College of Medicine
      Nonsan, South Chungcheong, South Korea