Browsing by Subject "Brain development"

Now showing 1 - 4 of 4
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    Expression of ribosomal protein L4 (rpL4) during neurogenesis and 5-azacytidine, (5AzC)-induced apoptotic process in the rat
    (Murcia : F. Hernández, 2002) Ueno, M.; Nakayama, Hiroyuki; Kajikawa, S.; Katayama, K.; Suzuki, K.; Doi, K.
    5-Azacytidine (5AzC) induces neuronal apoptosis in rat and mouse fetuses. 5AzC also induces apoptosis in undifferentiated PC12 cells, and ribosomal protein L4 (rpL4) mRNA expression increases prior to apoptosis. To clarify the roles of rpL4 during neurogenesis, we first examined the distribution of rpL4 mRNA in the developing rat brain by in situ hybridization and RT-PCR, and compared the results to the distribution of TUNEL- or PCNA-positive cells. rpL4 mRNA expression was strong in the ventricular zone (VZ), subventricular zone (SVZ), cortical plate (CP), cerebral cortex, granule cell layer (GCL), pyramidal cell layer (Py) and external granular layer (EGL) during embryonic and early postnatal days, and it was remarkably weakened thereafter. A lot of PCNApositive cells were observed in VZ, SVZ, and EGL during embryonic and early postnatal days, and such distribution of PCNA-positive cells was almost identical to rpL4 mRNA distribution. Only few TUNEL-positive cells were observed in VZ, SVZ, cerebral cortex, EGL, and hippocampus during embryonic and early postnatal days, and the regions with TUNEL-positive cells were not identical to rpL4 mRNA distribution. Next, the changes of rpL4 mRNA expression in the brain of 5AzC-treated rat fetuses were examined by in situ hybridization and RT-PCR. Apoptotic cells appeared at 9 to 24 hours after treatment (HAT). However, the rpL4 mRNA expression was unchanged during the apoptotic process. From the results, it is suggested that rpL4 would have certain roles in cell proliferation and differentiation during neurogenesis, but have no roles in 5AzC-induced apoptosis in the fetal brain.
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    Physiology and pathophysiology of nitric oxide in the nervous system, with special mention of the islands of Calleja and the circunventricular organs
    (Murcia : F. Hernández, 2002) Rodrigo, J.; Alonso, D.; Bentura, M.L.; Castro-Blanco, S.; Encinas, J.M.; Fernández, A.P.; Fernández-Vizarra, P.; Richart, A.; Santacana, M.; Serrano, J.; Martínez, A.
    Nitric oxide (NO) has been recognized as a key regulatory factor in many physiological processes, including central nervous system function, development, and phatophysiology. NO is produced by a class of enzymes known as NO synthases (NOS) and in normal adult animals only the neuronal isoform (nNOS) is detectable. During cortical development, nNOS was found at E14 in neuroblasts of the marginal zone and its expression raised to a zenith by P5, decreasing afterwards until reaching a steady level by P10. At that time, nNOS was found mainly in pyramidal neurons. Interestingly, the inducible isoform of the enzyme (iNOS) was also active from P3 to P7, but it disappeared almost completely by P20. The neurodegeneration observed during normal aging and following hypoxic accidents seems to be the result of cumulative free radical damage, and excessive production of NO may be at the basis of the cascade. After ischemic events we observed an elevation in the number of neurons expressing nNOS coincident with an elevation in Ca2+- dependent NOS activity for up to 120 min. After this period, nNOS activity began to decrease but it was substituted by a rapid increase in Ca2+-independent activity coincident with the histological appearance of previously undetectable iNOS-immunoreactive neurons. These increases in NO production were accompanied by specific patterns of protein nitration, a process that seems to result in loss of protein function. In particular, we observed a correlation between exposure to ischemia-reperfusion and nitration of cytochrome c. This process was coincident with the exit of the cytochrome from the mitochondria to the surrounding cytoplasm, an early event in neuronal apoptosis. Interestingly, most of the morphological and molecular changes associated with ischemic damage were prevented by treatment with inhibitors of NO production, indicating a clear path in the search for efficacious drugs in the battle against cerebrovascular accidents.
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    Rab family small GTPases-mediated regulation of intracellular logistics in neural development
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Shikanai, Mima; Yuzaki, Michisuke; Kawauchi, Takeshi
    Rab family small GTPases play essential roles in various cellular events via the regulation of intracellular logistics comprising a large number of membrane traffic pathways. Emerging evidence reveals the physiological roles of Rab proteins in several tissues, including developing brains. Many Rab proteins, such as Rab5, Rab6, Rab7, Rab8, Rab10, Rab11, Rab17 and Rab18, are shown to regulate neurite outgrowth in PC12 cells and/or axon and dendrite formation in primary cultured neurons. Recent studies have also revealed in vivo roles of several Rab family small GTPases in brain development and its related neurological disorders. In this review, we introduce the physiological function of Rab family proteins in neural development with particular focus on neurite outgrowth and neuronal migration.
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    Roles of Rho small GTPases in the tangentially migrating neurons
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Ito, Hidenori; Morishita, Rika; Tabata, Hidenori; Nagata, Koh-ichi
    Rho small GTPases are members of the Ras superfamily of monomeric 20~30 kDa GTP-binding proteins. These proteins function as molecular switches that regulate various cellular processes such as migration, adhesion and proliferation. Cycling between GDP-bound inactive and GTP-bound active forms is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs) and GDPdissociation inhibitors (GDIs). Among 20 different mammalian Rho GTPases identified to date, RhoA, Rac1 and Cdc42 have been most extensively investigated; regulation of migration, adhesion and proliferation by these proteins have been well documented in a variety of cell types, including neurons. In neurons, RhoA, Rac1 and Cdc42 are crucial for axon guidance, dendrite formation and spine morphogenesis, where molecular machineries required for cell migration and adhesion play essential roles. Recently, accumulating experimental data indicate the participation of Rho GTPases in neuronal cell migration. To establish the cortical lamination and synapse network formation, highly specialized modes of neuron migration are essential, which include 1) radial migration of excitatory pyramidal neurons along radial glial fibers, 2) tangential migration of GABAergic cortical (inhibitory) interneurons along emerging axon tracts and 3) chain migration of interneurons ensheathed in a glial network, which is observed only in olfactory bulb-directed adult neurogenesis. While roles of Rho GTPases in the radial migration have been well reviewed, knowledge of their functions in tangential migration and chain migration are fragmentary to date. In this review, we focus on the roles of Rho small GTPases and their related molecules in tangential migration, together with the possible application of the electroporation method to analyses for this mode of migration in embryonic and postnatal mouse brain.