摘要:

IN mammals, cytosine methylation is important for the regulation of gene expression and chromatin structure. Recently, we have found evidence indicating that the maintained DNA methyltransferase activity is critical for neuronal cell differentiation. In the present study, we have investigated the effect of the DNA methyltransferase inhibitor 5-azacytidine on gene regulation during nerve growth factor (NGF)-induced neuronal differentiation of PC12 cells. Expression of the helix–loop–helix proteins Id1, Id2 and Id3 was specifically reduced by NGF and this effect was blocked in 5-azacytidine-treated cells, concomitant with the inhibition of NGF-induced neuronal differentiation. Nuclear run-on and Id2 promoter analyses further demonstrated that the decreased transcription of Id proteins is at least in part dependent on the DNA methyltransferase activity. These findings indicate that Id proteins are downstream targets of the NGF transduction pathway. Moreover, these results suggest that therapeutic strategies using 5-azacytidine against certain types of tumors should be reconsidered because of the possible deleterious effects on neuronal cell function.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

THE effects of a nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on 2-deoxy-D-glucose (2-DG)-induced hyperphagia were investigated in rats. L-NAME dose-dependently inhibited 2-DG-induced eating in non-food-deprived rats, although the inactive isomer D-NAME had no effect. The inhibitory effects of L-NAME on 2-DG-induced hyperphagia were inhibited by co-administration of L-arginine. The neuronal NO synthase inhibitor 7-nitroin-dazole also inhibited 2-DG-induced hyperphagia. These results suggest that 2-DG-induced hyperphagia is linked with NO and that brain NO may participate in this hyperphagic model.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

MAGNOCELLULAR neurons in the paraventricular nucleus are resistant to excitotoxic cell damage. We tested the hypothesis that a modified post-synaptic response following NMDA receptor activation may underlie this resistance. Whole-cell recordings from hypothalamic slices showed that NMDA receptor activation caused dose-dependent depolarizations in both Type I (putative magnocellular) and Type II (putative parvocellular) neurons. Type II cells, however, were an order of magnitude more sensitive (10 nM) than Type I neurons (100 nM). The depolarizations recorded in Type II cells were also significantly greater (> 35% resulting in sodium channel inactivation) than those recorded in Type I neurons. This differential sensitivity of neurons to NMDA receptor activation may explain the selective resistance of magnocellular PVN neurons to excitatory neurotoxins.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

THE action of interleukin-1β (IL-1β) and its receptor antagonist IL-1ra were investigated on dual component, isolated AMPA and NMDA field excitatory postsynaptic potentials (EPSP) and on the induction and maintenance of long-term potentiation in the rat dentate gyrusin vitro. Perfusion with IL-1β (1 ng/ml) for 1 h had no significant effect on the dual component EPSP or the isolated AMPA-EPSP. In contrast IL-1β had a significant inhibitory effect on the isolated NMDA-EPSP amplitude (54 ± 7% at 1 h compared with controls;n= 9;p< 0.001). This effect was fully antagonized in the presence of 100 ng/ml IL-1 receptor antagonist. IL-1β also inhibited LTP of the dual component EPSP but had no effect on the maintenance phase when applied postinduction of LTP. This study demonstrates for the first time that the inhibitory effect of IL-1β on LTP in the dentate gyrus may be at least partially due to a block of post-synaptic NMDA receptors.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

FIRST generation, replication-defective adenoviral vectors are highly effective for gene transfer into the central nervous system, but the host's immune response limits the utility of this vector for possible therapy of neurological disease or long-term gene transfer studies in experimental animals. We have demonstrated the effectiveness of FK506 (tacrolimus), a powerful immunosuppressant that readily crosses the blood–brain barrier, in maintaining adenovirus-mediated reporter gene transfer following stereotaxic injection of the recombinant (AdCMVlacZ) into mouse striatum. After 28 days, β-galactosidase expression was reduced by 75% relative to day 10 in immunocompetent animals, accompanied by an inflammatory reaction in the region of transduced cells; however, in mice receiving daily s.c. injections of FK506, β-galactosidase activity was maintained at the 10 days post-injection level.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

SUBSTANCE P (SP) has been implicated in immune responses and could increase glutamate release, and inflammatory reactions are known to be able to potentiate ischemic damage. We have previously found that SP was over-expressed in cerebral ischemia and speculated that SP may play a role in exacerbating ischemic damage. In this study, we examined whether a neurokinin-1 (NK-1) receptor antagonist, SR140333, would have an effect on brain ischemia. Intracerebroventricular (i.c.v.) administration of SR140333 (30 μg) markedly reduced (37.1 ± 7.8%,p< 0.001) infarct volume measured 24 h after focal cerebral ischemia in the rat. The SR140333-treated group also exhibited a significantly improved neurological function reflected by the neurological deficit score. The results represented the first demonstration that a NK-1 receptor antagonist may be a novel type of drug for treatment of cerebral ischemia.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

SIMULTANEOUS quantification of the two major nitric oxide (NO) metabolites, nitrite and nitrate, was performed on mouse mesencephalic neuronsin vitro, in basal conditions or after excitatory stimuli. Measurements were made using both extracellular medium and cytosolic extracts. Basal metabolite levels were stable up to 5 min. Depolarization by high levels of potassium promptly increased extracellular nitrite (270% of basal, peak at 10 s) leaving intracellular levels unchanged. Glutamate receptor agonists caused a rapid increase in intracellular, but not extracellular, nitrite levels (240% of basal, peak at 30 s). Intracellular nitrate levels raised slowly after addition of potassium (215% of basal at 1 min) orN-methyl-D-aspartate (230% of basal at 5 min), but not after quisqualate. The different dynamic variations of the two NO metabolites point to the specificity of the activated metabolism according to the type of excitatory stimulus.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

MICROGLIAL cells are the intrinsic immunocompetent cells of the central nervous system, which are activated by brain tissue damage. In this paper we investigated the ability of endothelins (ETs), which are potent vasoconstrictors, to induce intracellular calcium signals in cultured microglia cells. Both endothelin-1 and endothelin-3 increased intracellular Ca2+concentration ([Ca2+]i). These [Ca2+]itransients were mimicked by BQ3020, an ETBreceptor agonist and blocked by BQ788, a selective ETBantagonist, respectively. The calcium signals induced by the endothelins persisted in Ca2+-free media. Transcripts encoding the ETBreceptor were detected in purified microglial cultures and cDNA fragments derived from ETBreceptor mRNA were amplified from 9% of electrophysiologically characterized microglial cells by the use of single-cell RT-PCR.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

THE secreted form of β-amyloid precursor protein (sAPPα) is released from neurons in an activity-dependent manner, and has been reported to modulate neuronal excitability in dissociated hippocampal neurons. We now report that sAPPα shifts the frequency dependence for induction of long-term depression of synaptic transmission (LTD) in hippocampal slices from adult rats. Whereas low frequency stimulation (1 Hz) of Schaffer collateral axons induced LTD of the post synaptic response of CA1 neurons in control slices, it did not induce LTD in slices pretreated with sAPPα. On the other hand, whereas a 10 Hz stimulation normally induced neither LTD or LTP, it did induce LTD in slices pretreated with sAPPα. sAPPα potentiated LTP induced by high frequency stimulation. sAPPα induced cGMP production in hippocampal slices, and pretreatment of slices with 8-bromo-cyclic GMP mimicked the effect of sAPPα on LTD suggesting a role for cyclic GMP in modulation of LTD. The data suggest an important role for sAPPα in modulation of synaptic plasticity in the hippocampus.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

SACCADIC eye and hand movements made to step displacements in target position were measured under conditions designed to dissociate the output of the ocular and manual motor systems. This was accomplished by having subjects look and point, either with or without vision of the hand (closed or open loop, respectively) at peripheral targets starting from independent initial positions. The results showed that the amplitude of open loop pointing responses increased in size when accompanied by saccades that were larger than the required hand movement. Providing the subject with visual feedback of the hand during the response or asking them to visually fixate caused this effect to disappear. Taken together, this pattern of results suggests that when vision of the hand is unavailable the programming of saccade metrics influences the control of simultaneously produced pointing movements in an on-line manner.

ISSN:0959-4965    

出版商:OVID    

年代:1997

数据来源: OVID