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        Histone deacetylase inhibitors promote neurosteroid-mediated cell differentiation and enhance serotonin-stimulated brain-derived neurotrophic factor gene expression in rat C6 glioma cells

        Morita, Kyoji,Gotohda, Takako,Arimochi, Hideki,Lee, Mi-Sook,Her, Song Wiley Subscription Services, Inc., A Wiley Company 2009 Journal of neuroscience research Vol.87 No.11

        <P>Progesterone treatment has previously been reported to promote the differentiation of glial cells probably through the production of 5α-reduced neurosteroids, resulting in the enhancement of serotonin-stimulated brain-derived neurotrophic factor (BDNF) gene expression, which is considered to contribute to the survival, regeneration, and plasticity of neuronal cells in the brain and hence has been suggested to improve mood disorders and other symptoms in depressive patients. Based on these previous observations, the effects on glial cells of histone deacetylase (HDAC) inhibitors, which are known as agents promoting cell differentiation, were examined using rat C6 glioma cells as a model for in vitro studies. Consequently, trichostatin A (TSA), sodium butyrate (NaB), and valproic acid (VPA) stimulated glial fibrillary acidic protein (GFAP) gene expression, and their stimulatory effects on GFAP gene expression were inhibited by treatment of these cells with finasteride, an inhibitor of the enzyme producing 5α-reduced neurosteroids. In addition, HDAC inhibitors enhanced serotonin-stimulated BDNF gene expression, the enhancement of which could be abolished by the inhibition of 5α-reduced neurosteroid production in the glioma cells. These results suggest that HDAC inhibitors may be able to promote the differentiation of rat C6 glioma cells through the production of 5α-reduced neurosteroids, resulting in the enhancement of serotonin-stimulated BDNF gene expression as a consequence of promoting their differentiation, indicating the possibility that differentiated glial cells may be implicated in preserving the integrity of neural networks as well as improving the function of neuronal cells in the brain. © 2009 Wiley-Liss, Inc.</P>

      • A distinct functional distribution of α and γ motoneurons in the rat trigeminal motor nucleus

        Morita-Isogai, Yukako,Sato, Hajime,Saito, Mitsuru,Kuramoto, Eriko,Yin, Dong Xu,Kaneko, Takeshi,Yamashiro, Takashi,Takada, Kenji,Oh, Seog Bae,Toyoda, Hiroki,Kang, Youngnam Springer-Verlag 2017 BRAIN STRUCTURE AND FUNCTION Vol.222 No.7

        <P>Gamma-motoneurons (gamma MNs) play a crucial role in regulating isometric muscle contraction. The slow jaw-closing during mastication is one of the most functional isometric contractions, which is developed by the rank-order recruitment of alpha-motoneurons (alpha MNs) in a manner that reflects the size distribution of alpha MNs. In a mouse spinal motor nucleus, there are two populations of small and large MNs; the former was identified as a population of gamma MNs based on the positive expression of the transcription factor estrogen-related receptor 3 (Err3) and negative expression of the neuronal DNA-binding protein NeuN, and the latter as that of alpha MNs based on the opposite pattern of immunoreactivity. However, the differential identification of alpha MNs and gamma MNs in the trigeminal motor nucleus (TMN) remains an assumption based on the size of cell bodies that were retrogradely stained with HRP. We here examined the size distributions of alpha MNs and gamma MNs in the dorsolateral TMN (dl-TMN) by performing immunohistochemistry using anti-Err3 and anti-NeuN antibodies. The dl-TMN was identified by immunopositivity for vesicular glutamate transporter-1. Immunostaining for choline acetyltransferase and Err3/NeuN revealed that the dl-TMN is composed of 65% alpha MNs and 35% gamma MNs. The size distribution of alpha MNs was bimodal, while that of gamma MNs was almost the same as that of the population of small alpha MNs , suggesting the presence of alpha MNs as small as gamma MNs. Consistent with the size concept of motor units, the presence of smaller jaw-closing alpha MNs was coherent with the inclusion of jaw-closing muscle fibers with smaller diameters compared to limb muscle fibers.</P>

      • KCI등재후보

        Multiple Movement AND D-LINKING

        Morita, Hisashi 대한언어학회 2003 언어학 Vol.11 No.2

        This paper aims to resolve problems with multiple movements of wh-phrases, particularly, in Bulgarian. The topic includes discussions of (ⅰ) why and how multiple movements are possible, (ⅱ) what kind of movement they are, that is, whether they are WH movement as Pesetsky (2000) argues or focus movement as Bo??kovi?? (1998) claims, and (ⅲ) why D-linked wh-Phrases can remain in situ. I will argue that multiple movement of wh-phrases is not WH but focus movement and will show that D-linked wh-phrases can omit their WH features due to Pragmatic support and, because of this, they can escape overt movement.

      • SCOPUSKCI등재

        Imaging features of Stafne bone defects on computed tomography: An assessment of 40 cases

        Morita, Lucas,Munhoz, Luciana,Nagai, Aline Yukari,Hisatomi, Miki,Asaumi, Junichi,Arita, Emiko Saito Korean Academy of Oral and Maxillofacial Radiology 2021 Imaging Science in Dentistry Vol.51 No.1

        Purpose: This study was performed to assess and describe the imaging features of 40 cases of Stafne bone defects (SBDs) on computed tomographic (CT) examinations. Materials and Methods: This study collected data, including age and sex, from 40 patients with SBDs who underwent CT exams. The imaging features of the SBDs were assessed in terms of their location, average size, the relationship of their contour with the cortical plate of the lingual mandible, bone margins, degree of internal density, shape, topographic relationship between the defect and the mandibular edge, the distance from the SBD to the base of the mandible, and the Ariji classification (type I, II, and III). Results: The average age was 57.3 years(range, 28-78 years), and the patients were predominantly male (70%). In all cases (100%), the posterior unilateral lingual SBD variant was observed. Within the Ariji classification, type I was the most common (60%). Among the most frequently observed radiographic characteristics were thick sclerotic bone margin across the entire defect contour, completely hypointense internal content, an oval shape, and continuity with the mandibular base with discontinuity of the mandibular edge. Conclusion: This study showed that posterior SBDs could present with an oval or rounded shape, complete hypodensity, and thick sclerotic margins. Likewise, SBDs could appear almost anywhere, with minor differences from the classic SBD appearance. It is fundamental for dental practitioners to know the imaging features of SBDs, since they are diagnosed primarily based on imaging.

      • Polyamines cause elevation of steroid 5α-reductase mRNA levels by suppressing mRNA degradation in C6 glioma cells.

        Morita, Kyoji,Lee, Mi-Sook,Her, Song,Nishibori, Naoyoshi Published for the International Federation for Cel 2014 Cell biology international Vol.38 No.10

        <P>Polyamines are widely distributed in living organisms, and considered to play a potential role in various cellular processes. The effects of polyamines on gene expression as well as cell proliferation have been suggested to be closely associated with the physiological and pathological functions. However, it seems necessary to investigate their potential roles in the regulation of cellular metabolism and functions. Previously, glial cells have been suggested to be involved in the protection and preservation of neuronal functions, probably through the production of neurotrophic factors in the brain. On the other hand, neuroactive 5α-reduced steroids promote glial cell differentiation, resulting in enhancement of their ability to produce brain-derived neurotrophic factor (BDNF). Based on these findings, polyamines are assumed to stimulate the expression of the gene encoding steroid 5α-reductase (5α-R), which can induce the production of neuroactive 5α-reduced steroids in glial cells. The effects of polyamines on 5α-R mRNA levels in C6 glioma cells were examined as a model experiment. In consequence, spermine (SPM) and spermidine (SPD), but not putrescine (PUT), have been shown to elevate 5α-R mRNA levels without activating the 5α-R promoter. Furthermore, SPM increased 5α-R mRNA levels under the conditions in which the mRNA biosynthesis was inhibited. Therefore, it can be speculated that polyamines increase 5α-R mRNA levels as a consequence of suppressing the degradation of mRNA.</P>

      • Progesterone pretreatment enhances serotonin-stimulated BDNF gene expression in rat c6 glioma cells through production of 5alpha-reduced neurosteroids.

        Morita, Kyoji,Her, Song Birkhäuser Boston 2008 Journal of molecular neuroscience Vol.34 No.3

        <P>Tricyclic antidepressants and selective serotonin reuptake inhibitors are considered in theory to induce the outflow of neurotransmitters, norepinephrine, and serotonin from the synapses as a consequence of inhibiting their reuptake into the nerve terminals, resulting in the stimulation of glial cells surrounding the synapses in the brain. Then, we have investigated the direct actions of neurotransmitters on glial cell metabolism and function using rat C6 glioma cells as an in vitro model system and suggested that these neurotransmitters induce their differentiation probably through the production of 5alpha-reduced neurosteroids. On the other hand, the stimulation of the glioma cells with serotonin has been reported to enhance brain-derived neurotrophic factor (BDNF) gene expression, which may be closely related to the beneficial effects of antidepressant drugs. In the present study, to evaluate BDNF expression in differentiated glial cells, the glioma cells were pretreated with progesterone, and the effect of serotonin on BDNF messenger RNA levels in these cells was examined. Progesterone pretreatment enhanced the stimulatory action of serotonin on BDNF gene expression, and the enhancement of serotonin action observed in the cells pretreated with progesterone was almost completely abolished by finasteride, an inhibitor of the enzyme involved in the production of 5alpha-reduced neurosteroids. These findings propose the possibility that neurosteroid-mediated glial cell differentiation may result in the enhancement of serotonin-stimulated BDNF gene expression, which is considered to contribute to the survival, regeneration, and plasticity of neuronal cells in the brain, and hence, leading to the improvement of mood disorders and other symptoms in depressive patients.</P>

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