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[en] Several theories have been proposed regarding pain transmission mechanisms in tooth. However, the exact signaling mechanism from odontoblasts to pulp nerves remains to be clarified. Recently, ATP-associated pain transmission has been reported, but it is unclear whether ATP is involved in tooth pain transmission. In the present study, we focused on the vesicular nucleotide transporter (VNUT), a transporter of ATP into vesicles, and examined whether VNUT was involved in ATP release from odontoblasts. We examined the expression of VNUT in rat pulp by RT-PCR and immunostaining. ATP release from cultured odontoblast-like cells with heat stimulation was evaluated using ATP luciferase methods. VNUT was expressed in pulp tissue, and the distribution of VNUT-immunopositive vesicles was confirmed in odontoblasts. In odontoblasts, some VNUT-immunopositive vesicles were colocalized with membrane fusion proteins. Additionally P2X_3, an ATP receptor, immunopositive axons were distributed between odontoblasts. The ATP release by thermal stimulation from odontoblast-like cells was inhibited by the addition of siRNA for VNUT. These findings suggest that cytosolic ATP is transported by VNUT and that the ATP in the vesicles is then released from odontoblasts to ATP receptors on axons. ATP vesicle transport in odontoblasts seems to be a key mechanism for signal transduction from odontoblasts to axons in the pulp
[en] Huntington's disease (HD) is an autosomal-dominant progressive neurodegenerative disorder that primarily affects medium spiny neurons within the striatum. HD is caused by inheritance of an expanded CAG repeat in the HTT gene, resulting in a mutant huntingtin (mHtt) protein containing extra glutamine residues. Despite the advances in understanding the molecular mechanisms involved in HD the preferential vulnerability of the striatum remains an intriguing question. This review discusses current knowledge that links altered mitochondrial dynamics with striatal susceptibility in HD. We also highlight how the modulation of mitochondrial function may constitute an attractive therapeutic approach to reduce mHtt-induced toxicity and therefore prevent the selective striatal neurodegeneration. - Highlights: • Mitochondrial dynamics is unbalanced towards fission in HD. • Excessive mitochondrial fragmentation plays a critical role in the selective vulnerability of the striatum in HD. • Therapeutic approaches aimed to inhibit mitochondrial fission could contribute to prevent striatal neurodegeneration in HD.
[en] We derive analytical formulas for the firing rate of integrate-and-fire neurons endowed with realistic synaptic dynamics. In particular, we include the possibility of multiple synaptic inputs as well as the effect of an absolute refractory period into the description. The latter affects the firing rate through its interaction with the synaptic dynamics.
[en] It has been recently reported that the centrosome of neurons does not have microtubule nucleating activity. Microtubule nucleation requires γ-tubulin as well as its recruiting proteins, GCP-WD/NEDD1 and CDK5RAP2 that anchor γ-tubulin to the centrosome. Change in the localization of these proteins during in vivo development of brain, however, has not been well examined. In this study we investigate the localization of γ-tubulin, GCP-WD and CDK5RAP2 in developing cerebral and cerebellar cortex with immunofluorescence. We found that γ-tubulin and its recruiting proteins were localized at centrosomes of immature neurons, while they were lost at centrosomes in mature neurons. This indicated that the loss of microtubule nucleating activity at the centrosome of neurons is due to the loss of γ-tubulin-recruiting proteins from the centrosome. RT-PCR analysis revealed that these proteins are still expressed after birth, suggesting that they have a role in microtubule generation in cell body and dendrites of mature neurons. Microtubule regrowth experiments on cultured mature neurons showed that microtubules are nucleated not at the centrosome but within dendrites. These data indicated the translocation of microtubule-organizing activity from the centrosome to dendrites during maturation of neurons, which would explain the mixed polarity of microtubules in dendrites
[en] Highlights: • miR-17-92 is highly related with hippocampal neurogenesis and mood behavior. • The expression of miR-17-92 cluster is regionally different in hippocampus. • miR-17-92 KO less affect development of neural progenitors in ventral hippocampus. • Interestingly, memory function was not altered by miR-17-92 KO. • These findings suggest the distinct function of regional expression of miR-17-92. It has been known that the dorsal and ventral areas of the dentate gyrus in the hippocampus have distinct roles in memory and mood behaviors. We previously reported that microRNA miR-17-92 regulates adult hippocampal neurogenesis and mood disorders. Here, we suggest that the miR-17-92 cluster is highly expressed in the ventral than the dorsal dentate gyrus in the adult mouse hippocampus. Deletion of miR-17-92 in the adult hippocampus only affects development of neural progenitors in the ventral dentate gyrus, and miR-17-92 knockout mice have no defects in memory functions. Our results suggest that regional expression of miR-17-92 in the dentate gyrus is associated with their distinct functions in hippocampal neurogenesis and related behaviors.
[en] The outbreak of Zika virus (ZIKV) and associated fetal microcephaly mandates efforts to understand the molecular processes of infection. Related flaviviruses produce noncoding subgenomic flaviviral RNAs (sfRNAs) that are linked to pathogenicity in fetal mice. These viruses make sfRNAs by co-opting a cellular exonuclease via structured RNAs called xrRNAs. We found that ZIKV-infected monkey and human epithelial cells, mouse neurons, and mosquito cells produce sfRNAs. The RNA structure that is responsible for ZIKV sfRNA production forms a complex fold that is likely found in many pathogenic flaviviruses. Mutations that disrupt the structure affect exonuclease resistance in vitro and sfRNA formation during infection. The complete ZIKV xrRNA structure clarifies the mechanism of exonuclease resistance and identifies features that may modulate function in diverse flaviviruses.
[en] Highlights: • Draxin deficiency led to abnormal projection of hippocampal mossy fibers. • Draxin receptors were expressed on granule cells dissociated from the dentate gyrus. • Draxin inhibited the growth of hippocampal mossy fibers in vitro. Lamina-specific afferent innervation of the mammalian hippocampus is critical for its function. We investigated the relevance of the chemorepellent draxin to the laminar projections of three principal hippocampal afferents: mossy fibers, entorhinal, and associational/commissural fibers. We observed that draxin deficiency led to abnormal projection of mossy fibers but not other afferents. Immunohistochemical analysis indicated that draxin is expressed in the dentate gyrus and cornu ammonis (CA) 3 at postnatal day 0, when dentate granule cells begin to extend mossy fibers towards CA3. Furthermore, a neurite growth assay using dissociated cells of the neonatal dentate gyrus revealed that draxin inhibited the growth of calbindin-D28k-expressing mossy fibers in vitro. Taken together, we conclude that draxin is a key molecule in the regulation of mossy fiber projections.
[en] Synapse plays an important role in signal exchange and information encoding between neurons. Electric and chemical synapses are often used to investigate the synchronization in electrical activities of neurons. In this paper, memristor is used to connect two neurons and the phase synchronization in electrical activities is discussed. Inter-spike interval (ISI) is calculated from the sampled time series for membrane potential, and the dependence of coupling intensity on phase synchronization of neuron is investigated and the effect of electromagnetic induction is considered. Furthermore, the synchronization stability of network is detected under noise; a statistical synchronization factor is also calculated. It is found synchronization can be enhanced under memristor coupling and appropriate noise is also helpful for synchronization stability.
[en] Melatonin, a lipophilic molecule that is mainly synthesized in the pineal gland, performs various neuroprotective functions. However, the detailed role and mechanisms of promoting neuronal differentiation remains limited. This study demonstrated that 10 μM melatonin led to significant increases in the proliferation and neurite outgrowth of PC12 cells. Increased expression of microtubule-associated protein 2 (MAP2, a neuron-specific protein) was also observed. However, luzindole (melatonin receptor antagonist) and PD98059 (MEK inhibitor) attenuated these increases. LY294002 (AKT inhibitor) inhibited melatonin-mediated proliferation in PC12 cells and did not affect melatonin-induced neural differentiation. The expression of p-ERK1/2/ERK1/2 was increased by melatonin treatment for 14 days in PC12 cells, whereas luzindole or PD98059 reduced the melatonin-induced increase. These results suggest that the activation of both the MEK/ERK and PI3K/AKT signaling pathways could potentially contribute to melatonin-mediated proliferation, but that only the MEK/ERK pathway participates in the melatonin-induced neural differentiation of PC12 cells. Altogether, our study demonstrates for the first time that melatonin may exert a positive effect on neural differentiation via melatonin receptor signalling and that the MEK/ERK1/2 signalling may act down stream from the melatonin pathway. - Highlights: • Melatonin improves the proliferation of PC12 cells. • Melatonin induces neural differentiation of PC12 cells. • Melatonin-mediated proliferation in PC12 cells relies on the ERK and AKT pathways. • Activation of ERK is essential for melatonin-induced neural differentiation of PC12.