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991.
Heterogeneous effects of antiepileptic drugs in an in vitro epilepsy model – a functional multineuron calcium imaging study 下载免费PDF全文
Yoshie Hongo Keiko Takasu Yuji Ikegaya Minoru Hasegawa Gaku Sakaguchi Koichi Ogawa 《The European journal of neuroscience》2015,42(2):1818-1829
Epilepsy is a chronic brain disease characterised by recurrent seizures. Many studies of this disease have focused on local neuronal activity, such as local field potentials in the brain. In addition, several recent studies have elucidated the collective behavior of individual neurons in a neuronal network that emits epileptic activity. However, little is known about the effects of antiepileptic drugs on neuronal networks during seizure‐like events (SLEs) at single‐cell resolution. Using functional multineuron Ca2+ imaging (fMCI), we monitored the activities of multiple neurons in the rat hippocampal CA1 region on treatment with the proconvulsant bicuculline under Mg2+‐free conditions. Bicuculline induced recurrent synchronous Ca2+ influx, and the events were correlated with SLEs. Other proconvulsants, such as 4‐aminopyridine, pentetrazol, and pilocarpine, also induced synchronous Ca2+ influx. We found that the antiepileptic drugs phenytoin, flupirtine, and ethosuximide, which have different mechanisms of action, exerted heterogeneous effects on bicuculline‐induced synchronous Ca2+ influx. Phenytoin and flupirtine significantly decreased the peak, the amount of Ca2+ influx and the duration of synchronous events in parallel with the duration of SLEs, whereas they did not abolish the synchronous events themselves. Ethosuximide increased the duration of synchronous Ca2+ influx and SLEs. Furthermore, the magnitude of the inhibitory effect of phenytoin on the peak synchronous Ca2+ influx level differed according to the peak amplitude of the synchronous event in each individual cell. Evaluation of the collective behavior of individual neurons by fMCI seems to be a powerful tool for elucidating the profiles of antiepileptic drugs. 相似文献
992.
993.
Yuji Yoshida Atsushi Ogata Sujin Kang Kousuke Ebina Kenrin Shi Satoshi Nojima Tetsuya Kimura Daisuke Ito Keiko Morimoto Masayuki Nishide Takashi Hosokawa Toru Hirano Yoshihito Shima Masashi Narazaki Hideki Tsuboi Yukihiko Saeki Tetsuya Tomita Toshio Tanaka Atsushi Kumanogoh 《Arthritis \u0026amp; Rheumatology》2015,67(6):1481-1490
994.
Keiko Kishimoto Jun Nomura Jacob Ellegood Keita Fukumoto Jason P. Lerch Daniel Moreno‐De‐Luca Thomas Bourgeron Kota Tamada Toru Takumi 《Genes to cells : devoted to molecular & cellular mechanisms》2017,22(5):436-451
Duplications of human chromosome 2q13 have been reported in patients with neurodevelopmental disorder including autism spectrum disorder. Nephronophthisis‐1 (NPHP1) was identified as a causative gene in the minimal deletion on chromosome 2q13 for familial juvenile type 1 nephronophthisis and Joubert syndrome, an autosomal recessive neurodevelopmental disorder characterized by a cerebellar and brain stem malformation, hypotonia, developmental delay, ataxia, and sometimes associated with cognitive impairment. NPHP1 encodes a ciliary protein, nephrocystin‐1, which is expressed in the brain, yet its function in the brain remains largely unknown. In this study, we generated bacterial artificial chromosome‐based transgenic mice, called 2q13 dup, that recapitulate human chromosome 2q13 duplication and contain one extra copy of the Nphp1 transgene. To analyze any behavioral alterations in 2q13 dup mice, we conducted a battery of behavioral tests. Although 2q13 dup mice show no significant differences in social behavior, they show deficits in spontaneous alternation behavior and fear memory. We also carried out magnetic resonance imaging to confirm whether copy number gain in this locus affects the neuroanatomy. There was a trend toward a decrease in the cerebellar paraflocculus of 2q13 dup mice. This is the first report of a genetic mouse model for human 2q13 duplication. 相似文献
995.
Fujimori H Asahina K Shimizu-Saito K Ikeda R Tanaka Y Teramoto K Morita I Teraoka H 《Journal of hepatology》2008,48(6):962-973
BACKGROUND/AIMS: Embryoid bodies (EBs) formed from embryonic stem cells (ESCs) differentiate into hepatocyte-like cells (HLCs), and are thus thought to be a useful cell source for drug testing and bioartificial liver. The aim of this study was to induce proliferation and function of ESC-derived HLCs in EBs using HLC-endothelial cell interaction. METHODS: EBs were cultured in the presence of vascular endothelial growth factor (VEGF) and/or VEGF receptor (VEGFR) inhibitors. To reproduce HLC-endothelial cell interaction, we overexpressed VEGF in ESC-derived HLCs under the control of Cyp7a1 gene in EBs. RESULTS: VEGF added to the cultured EBs increased the proliferation of ESC-derived endothelial cells, resulting in the promotion of proliferation and function of ESC-derived HLCs. In EBs, the VEGFR2 inhibitor suppressed expression of albumin and endothelial cell marker genes, whereas the inhibitor for both VEGFR1 and VEGFR2 suppressed expression of Cyp7a1 and hepatocyte growth factor (Hgf) genes. Upon exposure to VEGF, the endothelial cells in EBs increased Hgf mRNA expression. Forced VEGF expression in ESC-derived HLCs in EBs induced angiogenesis around the HLCs and resulted in an increase in the amount of HLCs. CONCLUSIONS: VEGF indirectly induces the proliferation and function of ESC-derived HLCs through VEGFR1 and VEGFR2 signaling in endothelial cells. 相似文献
996.
IGF-I receptor (IGF-IR) is involved in numerous biological functions via its major downstream signaling molecules, extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3'-kinase/Akt. The IGF-I-induced activation of ERK, but not that of Akt, is reportedly mediated by the transactivation of the epidermal growth factor receptor (EGFR) tyrosine kinase (TK). The mechanism for the EGFR-TK-dependent activation, however, still remains largely unknown. We found that an oral carcinoma cell line overexpressing EGFR, Ca9-22, exhibited IGF-I-induced activation of both Akt and ERK, but that only the latter was significantly decreased by a specific inhibitor of EGFR-TK, tyrphostin AG1478. In this report we provide evidence for the existence in this cell line of a novel mechanism by which IGF-I induces ERK activation in a manner that is dependent on the basal level of EGFR-TK activity, but is independent of receptor transactivation. In addition, we show that c-Raf kinase is likely to be a key regulator of this mechanism. The elucidation of such a unique mechanism involving cross-talk between EGFR and heterologous receptors may shed additional light on the clinical use of EGFR-TK inhibitors in antitumor therapies. 相似文献
997.
998.
Urao N Inomata H Razvi M Kim HW Wary K McKinney R Fukai T Ushio-Fukai M 《Circulation research》2008,103(2):212-220
Bone marrow (BM) is the major reservoir for endothelial progenitor cells (EPCs). Postnatal neovascularization depends on not only angiogenesis but also vasculogenesis, which is mediated through mobilization of EPCs from BM and their recruitment to the ischemic sites. Reactive oxygen species (ROS) derived from Nox2-based NADPH oxidase play an important role in postnatal neovascularization; however, their role in BM and EPC function is unknown. Here we show that hindlimb ischemia of mice significantly increases Nox2 expression and ROS production in BM-mononuclear cells (BMCs), which is associated with an increase in circulating EPC-like cells. Mice lacking Nox2 show reduction of ischemia-induced flow recovery, ROS levels in BMCs, as well as EPC mobilization from BM. Transplantation of wild-type (WT)-BM into Nox2-deficient mice rescues the defective neovascularization, whereas WT mice transplanted with Nox2-deficient BM show reduced flow recovery and capillary density compared to WT-BM transplanted control. Intravenous infusion of WT- and Nox2-deficient BMCs into WT mice reveals that neovascularization and homing capacity are impaired in Nox2-deficient BMCs in vivo. In vitro, Nox2-deficient c-kit+Lin- BM stem/progenitor cells show impaired chemotaxis and invasion as well as polarization of actins in response to stromal derived factor (SDF), which is associated with blunted SDF-1-mediated phosphorylation of Akt. In conclusion, Nox2-derived ROS in BM play a critical role in mobilization, homing, and angiogenic capacity of EPCs and BM stem/progenitor cells, thereby promoting revascularization of ischemic tissue. Thus, NADPH oxidase in BM and EPCs is potential therapeutic targets for promoting neovascularization in ischemic cardiovascular diseases. 相似文献
999.
Yokoyama M Nakahara K Kojima M Hosoda H Kangawa K Murakami N 《European journal of endocrinology / European Federation of Endocrine Societies》2005,152(1):155-160
OBJECTIVES: Ghrelin has recently been isolated from rat and human stomach as an endogenous ligand for the growth hormone (GH) secretagog receptor. Using beagle dogs, we investigated the distribution of ghrelin in the stomach and its possible role. METHODS: We examined: (i) GH release in response to ghrelin injection (0.5 or 5 microg/kg, i.v.), (ii) gastric localization of ghrelin-immunostained cells, (iii) changes in daily food consumption after ghrelin injection (3, 10, and 20 microg/kg, i.v.), (iv) plasma ghrelin levels under regular, but restricted feeding conditions, and (v) variations in plasma ghrelin levels in relatively lean, normal and obese dogs. RESULTS: Administration of ghrelin to dogs promptly increased circulating GH concentrations, although this effect was transitory and was maintained for only 20 min. Ghrelin was localized in the stomach fundus and body, but none was detected in either the pylorus or cardia. Administration of ghrelin at a dose of 20 microg/kg increased the daily food intake of beagle dogs. Plasma ghrelin levels peaked just before meal times, and then returned to basal levels. Obese dogs had higher plasma ghrelin levels than did normal and lean dogs. CONCLUSIONS: These results indicate that ghrelin is a potent GH secretagog in dogs. The distribution of ghrelin-immunoreactive cells in the canine stomach resembles that of both the murine and human stomach. Ghrelin participates in the control of feeding behavior and energy homeostasis in dogs and may, therefore, be involved in the development of obesity. 相似文献
1000.
Kazuya Kanemaru Hideyuki Yoshioka Takashi Yagi Takuma Wakai Koji Hashimoto Yuichiro Fukumoto Keiko Suzuki Toru Tateoka Hirofumi Kazama Hiroyuki Kinouchi 《Interventional neuroradiology》2015,21(1):88-93
Dural arteriovenous fistula (DAVF) involving the hypoglossal canal is rare but increasingly reported. To achieve complete obliteration without a procedure-related complication, understanding of the precise anatomy of this DAVF is essential. Here, we describe a 72-year-old man who underwent selective intra-arterial injection computed tomography angiography which allowed us to understand the detailed anatomy of the complex DAVF regarding access routes and the target regions for transvenous embolization (TVE). With the aid of this novel neuroimaging technique successful target TVE was achieved safely and completely. 相似文献