摘要:

3-NITROPROPIONIC acid (3-NP) is a mitochondrial toxin which interferes with ATP synthesis. Accidental ingestion of 3-NP by humans as well as other mammals results in neuronal degeneration within the basal ganglia and movement dysfunction characterized by dystonia, chorea, and hypokinesia. The selective degeneration of structures of the basal ganglia occurs despite the non-selective impairment of energy metabolism throughout the brain and body. These effects of 3-NP are shared with the genetic disorder Huntington's disease (HD), which is characterized by progressive neurodegeneration of the basal ganglia and choreic motor dysfunction. These similarities have prompted further investigation of 3-NP as an animal model of HD. Metabolic compromise with 3-NP causes neurodegeneration that involves three interacting processes: energy impairment, excitotoxicity, and oxidative stress. This triplet of cooperative pathways of neurodegeneration helps to explain 3-NP's regional selectivity of neurotoxicity to the basal ganglia. This mini-review will focus on the actions of 3-NP and the related compound, malonic acid (MA), in the central nervous system, with an emphasis on the more current findings regarding their mechanisms of action.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ACTIVITY of calpains and caspase-3 inferred from proteolysis of the cytoskeletal protein α-spectrin into signature spectrin breakdown products (SBDPs) was used to provide the first systematic and simultaneous comparison of changes in activity of these two families of cysteine proteases after traumatic brain injury (TBI) in rats. Distinct regional and temporal patterns of calpain/caspase-3 processing of α-spectrin were observed in brain regions ipsilateral to the site of injury after TBI, including large increases of 145 kDa calpain-mediated SBDP in cortex (up to 30-fold), and enduring increases (up to 2 weeks) of 145 kDa SBDP in hippocampus and thalamus. By contrast, 120 kDa caspase-3-mediated SBDP was absent in cortex and showed up to a 2-fold increase in hippocampus and striatum at early (hours) after TBI. Future studies will clarify the pathological significance of large regional differences in activation of calpain and caspase-3 proteases after TBI.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ALL important neuropathological features like neurodegeneration and amyloid deposition occur similarly in familial and in sporadic Alzheimer's disease (AD) patients, suggesting a common pathogenetic mechanism. We investigated whether defective vulnerabilty to the induction of the apoptotic cell death pathway might be one of the underlying mechanisms leading to progressive cell death in sporadic AD. Our test could prove useful in supporting the diagnosis of AD and in predicting individuals predisposed to AD.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

WE recently demonstrated that centrally administered melatonin at low doses inhibits the induction of gastric lesions by water-immersion restraint stress. To investigate the mechanism of the potent anti-ulcer action of melatonin, the central nervous system (CNS) effects of melatonin on gastric acid and pepsin secretion were studied in conscious pylorus-ligated rats. Intracisternal(i.c.) melatonin (1–100 ng) dose-dependently decreased acid and pepsin output, while a higher i.p. dose (1 μg) had no inhibitory effect. The i.c. melatonin did not change serum gastrin concentrations. Serum melatonin concentrations at 1 and 4 h after i.c. administration of 10–100 ng melatonin did not differ from those in rats receiving i.c. vehicle. The present results suggest that melatonin administered centrally modulates the secretion of gastric acid and pepsin which may explain, at least in part, the protective, anti-stress role of melatonin in the gastric mucosa observed in our previous study.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A new faster paradigm to measure the duration of auditory sensory memory, as indexed by mismatch negativity (MMN) suppression to stimuli presented at increasing inter-stimulus intervals (ISI), is proposed. Trains of three stimuli were delivered at very short ISI (300 ms). The inter-train interval varied according to the memory probe interval (MPI) tested. Trains started randomly with a deviant or standard stimulus (50% each), with their event-related brain potentials subtracted to obtain the MMN. The new paradigm provided MMNs identical to the conventional one at MPIs of 0.4 and 4.0 s in young subjects, and revealed MMN suppression when the MPI was increased to 5.0 s in older subjects. The new paradigm estimates auditory sensory memory duration in one-third the time of conventional MMN.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

THE conversion of normal, protease sensitive prion protein (PrP-sen) to the abnormal protease-resistant form (PrP-res) is of central importance in the pathogenesis of scrapie and other transmissible spongiform encephalopathies. In the present study, the effects of reduction of the disulfide bond on the PrP-sen to PrP-res conversion in a cell-free system were examined. The addition of the disulfide reducing agent dithiothreitol inhibited the cell-free conversion reaction with an IC50of 2–2.5 mM. Separate pretreatment of either PrP-sen or PrP-res with dithiothreitol and an alkylating agent also inhibited the conversion reaction. Results of this study show that preservation of the disulfide bond is important in the conversion of PrP-sen to PrP-res.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

THE i.v. self-administration by rats of a polydrug combination of cocaine and heroin was explored. The rewarding efficacies of a range of cocaine doses (0.25–8 mg/kg/ injection) alone or in combination with heroin (12.5 or 25 μg/kg/injection) were compared using a progressive ratio (PR) schedule of reinforcement. Breaking points (BP) for one group of rats were determined at each dose of cocaine alone and for two other groups at each of the same cocaine doses plus one of the heroin doses, respectively. The cocaine-heroin combination was associated with higher BPs than cocaine alone at all doses of cocaine. These data demonstrate that cocaine-heroin combinations (speedballs) are more rewarding than the identical doses of cocaine alone. Some possible mechanisms by which heroin increases cocaine reward are discussed.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

REISSNER'S membrane forms a partition between the endolymphatic and perilymphatic cochlear compartments. Expression of the P2X2receptor subunit which assembles to form ATP-gated ion channels was detected in guinea-pig Reissner's membrane using the reverse transcription polymerase chain reaction (RT-PCR). The P2X2 receptor subunit protein was localized to the epithelial cells which line the endolymphatic surface of Reissner's membrane using confocal immunofluorescence. The P2X receptor expression in Reissner's membrane was functionally confirmed using whole-cell voltage-clamp. An inwardly rectifying conductance was activated in Reissner's membrane epithelial cells in the presence of extracellular ATP (100 μM). This conductance had a pharmacological profile compatible with the P2X2receptor designation, but exhibited substantial desensitisation which may be attributable to additional P2X receptor subunits. This study indicates that extra-cellular ATP, a humoral factor within scala media, acts via ATP-gated ion channels expressed by Reissner's membrane epithelial cells to decrease the driving force for sound transduction.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

THE purpose of this study was to extend previous findings of changes in magnetic flux amplitude associated with neuronal currents in the human auditory cortex in response to two-tone stimuli selected from a tone-onset time (TOT) continuum. The results replicated previous findings byindicating a close correspondence between N1m field strength functions and individual perceptual identification curves. In a second experiment event-related fields were recorded in response to two-tone stimuli in which the two sinusoid components always started simultaneously, yet they showed the same energy envelope as the TOT stimuli (amplitude modulated (AM) tokens). The results showed that N1m modulation as a function of TOT could not be accounted for by an effect of AM. The findings suggest that discontinuities in N1m field amplitudefunctions were the result of interactions between two populations of active neurons each displaying distinct average sound frequencypreferences.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

IT has been controversial whether the perception of illusory contours arise from higher level cognitive mechanisms that require attention or from early preattentive visual processes. We studied three patients with left spatial neglect who were unable to detect the left inducers of Kanizsa illusory figures in a same/different judgment task but nonetheless showed implicit perception of the figures in a midpoint judgment, in that they made identical bisection for figures with illusory or real contours but very different bisection for other spatially discontinuous figures that did not yield illusory fillingin. Grouping and filling-in mechanisms can thus occur without explicit detection of, or attention to, the inducing features, consistently with the hypothesis that they involve preattentive visual processes.

ISSN:0959-4965    

出版商:OVID    

年代:1998

数据来源: OVID