ISSN:0959-4965    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The effect of huperzine A (HupA) on oxygen–glucose deprivation (OGD)-induced injury was investigated in the rat pheochromocytoma cell line PC12. OGD for 3 h and reoxygenation for 24 h triggered apoptosis characterized by chromatin condensation, nucleus fragmentation and DNA laddering. The temporal profile of c-jun,p53,bcl-2andbaxmRNA after OGD indicated that these genes played important roles in apoptosis. Pre-incubation of the cells for 2 h with 1 μM HupA significantly attenuated apoptosis. The same treatment also reduced the up-regulation of c-junandbaxas well as the down-regulation ofbcl-2. These data suggest the ability of HupA to attenuate apoptosis induced by OGD may result from its capability to alter the expression of apoptosis-related genes.

ISSN:0959-4965    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Pro-inflammatory cytokines have been shown to be involved in the genesis, persistence, and severity of neuropathic pain following nerve injury. The transcription factor, nuclear factor-kappa B (NF-κB), plays a pivotal role in regulating pro-inflammatory cytokine gene expression. To elucidate the role of NF-κB in the pathogenesis of neuropathic pain, using a gene-based approach of NF-κB decoy, we tested whether the activated NF-κB affected pain behavior via the expression of inflammatory mediators. Single endoneurial injections of NF-κB decoy, at the site of nerve lesion, significantly alleviated thermal hyperalgesia for up to 2 weeks and suppressed the expression of mRNA of the inflammatory cytokines, iNOS, and adhesion molecules at the site of nerve injury. This finding suggests that a perineural inflammatory cascade, that involves NF-κB, is involved in the pathogenesis of neuropathic pain.

ISSN:0959-4965    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We examined the immunoreactivity of ubiquitin-binding protein p62 and its association with ubiquitin (Ub), α-synuclein, and paired helical filament (PHF)-tau in the affected brain areas of human tauopathies and synucleinopathies. Ubiquitin-binding protein p62 is a widely expressed protein that can bind to Ub noncovalently and is involved in several signalling pathways, making p62 a candidate regulator of Ub-mediated proteolysis. We show that p62 immunoreactivity co-localizes with neuronal and glial Ub-containing inclusions in Alzheimer's disease, Pick's disease, dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy. This is the first demonstration of a common protein component, apart from Ub, that is present in both PHF-tau and α-synuclein inclusions. In both tauo- and synucleinopathies, the staining patterns for p62 and Ub were markedly similar, suggesting that a common mechanism which requires interaction of p62 and Ub contributes to the formation of PHF-tau and α-synuclein inclusions.

ISSN:0959-4965    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We assessed the effects of intravenous morphine on the wind-up of nociceptive neurons of the spinal trigeminal nucleus oralis (Sp5O). Extracellular recordings of Sp5O nociceptive convergent neurons were performed in intact halothane-anesthetized rats. Wind-up of C-fiber-evoked responses was elicited by repetitive electrical stimulation (train of 16 shocks, 0.66 Hz) of their receptive field at C-fiber intensity (3 times the threshold). Wind-up was tested for its sensitivity to morphine (6 mg/kg,i.v.), and the specificity of the effects was verified with naloxone (0.4 mg/kg, i.v.). Nineteen convergent neurons displaying wind-up were recorded. Morphine reduced the wind-up of all but one. In five cases, notwithstanding a reduced wind-up, the neuronal response evoked by the first stimulus in the train (initial input) was unexpectedly increased. Naloxone always antagonized morphine inhibitory effects on the wind-up. When administered systemically, morphine reduced the wind-up of trigeminal nociceptive neurons. This inhibitory effect occurred independently of morphine's ability to affect the initial C-fiber-evoked input. Our findings support the idea that systemic morphine probably blocks wind-up by acting at opioid receptors located postsynaptically to nociceptive primary afferents.

ISSN:0959-4965    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Norepinephrine (NE) reduces the release of neuropeptides from central terminals of primary afferent neurones by presynaptic inhibition. We investigated whether NE also affects stimulus-induced intracutaneous calcitonin gene-related peptide (CGRP) and secondary prostaglandin E2(PGE2) release. For comparison, κ-opioid effects were examined. Antidromic electrical nerve stimulation resulted in significant increases in the release of CGRP and PGE2. The PGE2release was prevented by selective activation of α2-adrenoceptors whereas the CGRP release was not changed. In contrast, selective κ-opioid receptor activation diminished electrically evoked release of both CGRP and PGE2. We conclude that NE affected stimulated PGE2release via α2-adrenoceptors on cells other than cutaneous afferents while κ-opioid receptors are expressed in peripheral terminals of cutaneous afferents and their activation reduced CGRP release and secondary PGE2formation.

ISSN:0959-4965    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Parietal neurons have retinotopic receptive fields whose response is modulated by eye gaze signals. We examined the role of eye position and eye movement direction on visual extinction in three patients with parietal damage and left neglect, characterized by impaired perception of contralesional field stimuli despite intact visual cortex. Patients tracked a horizontally moving fixation point, while discriminating fine changes at the fixated point and detecting more salient targets flashed on either side of fixation. Eye position modulated extinction, with worse detection of left field targets during eccentric fixation towards the left. Direction of eye movement also modulated extinction, with worse detection of left targets during rightward scanning. These results demonstrate that extinction in contralesional field is influenced by extra-retinal factors related to eye position and eye movements, consistent with a convergence of these signals in parietal cortex.

ISSN:0959-4965    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We examined how transient cerebral ischemia affects the mRNA expression, and the immunoreactive distribution, of the somatostatin type 2 (sst2) receptor in the adult rat hippocampus. Following reperfusion, sst2 mRNA levels increased significantly in the CA1 region by 3 h, and were also increased in the CA3 and CA4/hilus subfields at 6 and 12 h. At 24 h, however, sst2 receptor mRNA levels returned to baseline throughout the hippocampus. At the protein level, we found the regional immunoreactivity of the sst2a receptor was maintained, or slightly elevated, throughout the hippocampus at 6 h, but not different from control at 24 h. These results suggest that sst2 receptors maintain their normal distribution and prevalence in the post-ischemic hippocampus before the deterioration of the vulnerable CA1 neurons. Thus, they represent attractive targets for neuroprotective interventions.

ISSN:0959-4965    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Apoptosis participates in the development of the nervous system and in neurodegeneration. The aim of this study was to investigate the mechanisms of detachment of neuronal cells from the extracellular matrix (ECM) during apoptosis. Detachment of Ntera2 neuronal cells was accompanied by decreased surface expression of the β1 integrin and redistribution of proteins from focal adhesions (FA). FA proteins were cleaved in a discrete sequence: p130cas, then paxillin, then talin. Caspase inhibition prevented detachment and cleavage of paxillin and p130cas, whilst calpain inhibition blocked talin cleavage. Neuronal cells therefore detach as a result of redistribution and caspase-dependent cleavage of focal adhesion proteins. Cleavage occurs sequentially such that critical ECM-integrin survival signalling cascades are severed before disruption of focal adhesion–cytoskeletal links.

ISSN:0959-4965    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The expression of prepro-orexin (PPO) mRNA in the rat brain was investigated byin situhybridization histochemistry. In the lateral and posterior hypothalamic areas, which are considered to produce exclusively PPO mRNA, we found high levels of PPO mRNA expressions. We also localized PPO mRNA hybridization signals at lower levels around the lateral ventri- cles, the third and fourth ventricle. Cellular analysis by emulsion autoradiography revealed the expression of PPO mRNA in the ependymal cell layer. Our results demonstrate that beside the lateral and posterior hypothalamus PPO mRNA is expressed in ependymal cells.

ISSN:0959-4965    

出版商:OVID    

年代:2001

数据来源: OVID