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| 2. |
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| 3. |
- Abbas, Abdul-Karim, 1959, et al.
(författare)
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Persistent LTP without triggered protein synthesis.
- 2009
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Ingår i: Neuroscience research. - : Elsevier BV. - 0168-0102. ; 63:1, s. 59-65
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Tidskriftsartikel (refereegranskat)abstract
- Protein synthesis is believed to be involved in stabilizing synaptic plasticity. Effects lasting longer than about 2-3h are considered to require synthesis of new proteins, implying a functional separation between early (E) and late (L) components. However, the issue of constitutive vs. new protein synthesis is still unclear, especially in young animals. Here, we examined the effects of two protein synthesis inhibitors, anisomycin and emetine, on long-term-potentiation (LTP) in CA1 area of hippocampal slices from 12- to 20-day-old rats. Either drug was applied from -30 min to +30 min with respect to LTP induction, a time window previously reported to be critical. However, the LTP remained stable under the entire recording period of 4h (anisomycin), or 8h (emetine). Proper preparation of emetine solution was evidenced by the fact that, in separate experiments, prolonged treatment with emetine gradually blocked baseline responses. Although no corresponding effect was observed with anisomycin, the drug was judged to be potent by its ability to inhibit yeast growth. The ability of anisomycin to inhibit protein synthesis was further confirmed by radiolabeling experiments assessing the degree of leucine incorporation. Our data suggest that LTP up to at least 8h is not dependent on triggered protein synthesis but can be attained by utilizing proteins already available at induction time.
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| 4. |
- Abbas, Abdul-Karim, 1959, et al.
(författare)
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S-sulfo-cysteine is an endogenous amino acid in neonatal rat brain but an unlikely mediator of cysteine neurotoxicity.
- 2008
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Ingår i: Neurochemical research. - : Springer Science and Business Media LLC. - 0364-3190 .- 1573-6903. ; 33:2, s. 301-7
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Tidskriftsartikel (refereegranskat)abstract
- S-sulfo-cysteine (SSC) is an agonist of glutamate receptors which could be involved in cysteine-induced neurotoxicity. Here we analyzed SSC by HPLC and demonstrated that the concentration of SSC in cortex of cysteine-injected rats increased to 1.4 microM, about four times the value of control rats. The neurotoxic effect of SSC was evaluated in slice cultures of rat hippocampus and compared to NMDA and cysteine. The neurotoxicity threshold of SSC was well above the tissue concentration. Our results show that SSC increases in neonatal rat brain after cysteine injection but reaches a tissue concentration far below concentrations that induce neurotoxicity in vitro. Thus, even if all the tissue SSC after cysteine injection was extracellular it would be below the threshold for toxicity, indicating that SSC is not a main excitotoxin involved in cysteine toxicity.
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| 7. |
- Faijerson, Jonas, 1977, et al.
(författare)
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Adult neural stem/progenitor cells reduce NMDA-induced excitotoxicity via the novel neuroprotective peptide pentinin.
- 2009
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Ingår i: Journal of neurochemistry. - 1471-4159. ; 109:3, s. 858-66
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Tidskriftsartikel (refereegranskat)abstract
- Although the potential of adult neural stem cells to repair damage via cell replacement has been widely reported, the ability of endogenous stem cells to positively modulate damage is less well studied. We investigated whether medium conditioned by adult hippocampal stem/progenitor cells altered the extent of excitotoxic cell death in hippocampal slice cultures. Conditioned medium significantly reduced cell death following 24 h of exposure to 10 microM NMDA. Neuroprotection was greater in the dentate gyrus, a region neighboring the subgranular zone where stem/progenitor cells reside compared with pyramidal cells of the cornis ammonis. Using mass spectrometric analysis of the conditioned medium, we identified a pentameric peptide fragment that corresponded to residues 26-30 of the insulin B chain which we termed 'pentinin'. The peptide is a putative breakdown product of insulin, a constituent of the culture medium, and may be produced by insulin-degrading enzyme, an enzyme expressed by the stem/progenitor cells. In the presence of 100 pM of synthetic pentinin, the number of mature and immature neurons killed by NMDA-induced toxicity was significantly reduced in the dentate gyrus. These data suggest that progenitors in the subgranular zone may convert exogenous insulin into a peptide capable of protecting neighboring neurons from excitotoxic injury.
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| 8. |
- Fredlund, Kerstin, 1954, et al.
(författare)
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Absorption of zinc and retention of calcium: dose-dependent inhibition by phytate
- 2006
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Ingår i: Journal of Trace Elements in Medicine and Biology. - : Elsevier BV. - 0946-672X. ; 20:1, s. 49-57
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Tidskriftsartikel (refereegranskat)abstract
- The dose-dependent inhibitory effect of sodium phytate (myo-inositol-hexaphosphate) on absorption of zinc and retention of calcium was studied in man. No systematic study of this dose-response effect has been reported to this time. Forty subjects were served meals containing white wheat rolls without/with additions of phytate. Ten subjects were given test meals containing one or two of the studied levels of phytate and in addition all subjects were served meals to which no phytate was added. The zinc content was 3.1 mg (47 mu mol) and the calcium content 266 mg (6.6 mmol). The rolls were labelled extrinsically with radioisotopes, Zn-65 and Ca-47, and whole-body retention of both minerals was measured. Totally 105 meals were served, 36 meals in which no phytate was added and 9-10 meals on each level of phytate. The zinc absorption in meals to which either 0, 25, 50, 75, 100, 140, 175 or 250 mg of phytate-P (0, 134, 269, 403, 538, 753, 941 or 1344 mu mol phytate) had been added was 22%, 16%, 14%, 11%, 7%, 7%, 7% and 6%, respectively (mean values). The addition of 50 mg phytate-P or more significantly decreased zinc absorption (p = 0.01) as compared to absorption from the test meals with no added phytate. The calcium retention at day 7 in the same meals was 31%, 28%, 27%, 26%, 22%, 19%, 14% and 11% (mean values). The addition of 100 mg phytate-P or more significantly decreased calcium retention (p = 0.03) compared to the test meals with no added phytate. It was concluded that the inhibitory effect of phytate on the absorption of zinc and the retention of calcium was dose dependent.
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| 9. |
- Guy, Yifat, et al.
(författare)
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Determination of zeta-potential and tortuosity in rat organotypic hippocampal cultures from electroosmotic velocity measurements under feedback control.
- 2009
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Ingår i: Analytical chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 81:8, s. 3001-7
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular translational motion in the brain is generally considered to be governed by diffusion and tortuosity. However, the brain as a whole has a significant zeta-potential, thus translational motion is also governed by electrokinetic effects under a naturally occurring or applied electric field. We have previously measured zeta-potential and tortuosity in intact brain tissue; however, the method was tedious. In this work, we use a four-electrode potentiostat to control the potential difference between two microreference electrodes in the tissue, creating a constant electric field. Additionally, some alterations have been made to simplify our previous procedure. The method entails simultaneously injecting two 70 kDa dextran conjugated fluorophores into rat organotypic hippocampal cultures and observing their mobility using fluorescence microscopy. We further present two methods of data analysis: regression and two-probe analysis. Statistical comparisons are made between the previous and current methods as well as between the two data analysis methods. In comparison to the previous method, the current, simpler method with data analysis by regression gives statistically indistinguishable mean values of zeta-potential and tortuosity, with a similar variability for zeta-potential, -21.3 +/- 2.8 mV, and a larger variability for the tortuosity, 1.98 +/- 0.12. On the other hand, we find that the current method combined with the two-probe analysis produces accurate and more precise results, with a zeta-potential of -22.8 +/- 0.8 mV and a tortuosity of 2.24 +/- 0.10.
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| 10. |
- Guy, Yifat, et al.
(författare)
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Determination of zeta-potential in rat organotypic hippocampal cultures.
- 2008
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Ingår i: Biophysical journal. - : Elsevier BV. - 1542-0086 .- 0006-3495. ; 94:11, s. 4561-9
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Tidskriftsartikel (refereegranskat)abstract
- zeta-potentials of entities such as cells and synaptosomes have been determined, but zeta of brain tissue has never been measured. Electroosmotic flow, and the resulting transport of neuroactive substances, would result from naturally occurring and experimentally or clinically induced electric fields if zeta is significant. We have developed a simple method for determining zeta in tissue. An electric field applied across a rat organotypic hippocampal slice culture (OHSC) drives fluorescent molecules through the tissue by both electroosmotic flow and electrophoresis. Fluorescence microscopy is used to determine each molecule's velocity. Independently, capillary electrophoresis is used to measure the molecules' electrophoretic mobilities. The experiment yields zeta-potential and average tissue tortuosity. The zeta-potential of OHSCs is -22 +/- 2 mV, and the average tortuosity is 1.83 +/- 0.06. In a refined experiment, zeta-potential is measured in various subregions. The zeta-potentials of the CA1 stratum pyramidale, CA3 stratum pyramidal, and dentate gyrus are -25.1 +/- 1.6 mV, -20.3 +/- 1.7 mV, and -25.4 +/- 1.0 mV, respectively. Simple dimensional arguments show that electroosmotic flow is potentially as important as diffusion in molecular transport.
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| 11. |
- Hultman, Karin, 1980, et al.
(författare)
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Maternal taurine supplementation in the late pregnant rat stimulates postnatal growth and induces obesity and insulin resistance in adult offspring
- 2007
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Ingår i: J Physiol. ; 579(Pt 3):Jan 11, s. 823-33
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Tidskriftsartikel (refereegranskat)abstract
- An adequate supply of taurine during foetal life is important for normal beta-cell development and insulin action and an altered availability of taurine may program glucose metabolism in utero and result in type 2 diabetes in adult age. We examined whether maternal taurine supplementation in late pregnant rats affects postnatal growth, adult body composition, insulin sensitivity and endogenous insulin secretion in intra-uterine growth restricted (IUGR) and normal offspring. Uterine artery ligation or sham operations were performed on gestational day (GD) 19. Taurine supplementation was given to half of the dams from GD 18 until term resulting in four groups of offspring: sham (n= 22), sham/taurine (n= 22), IUGR (n= 22) and IUGR/taurine (n= 24). The offspring were studied at 12 wks of age. In offspring with normal birth weight, foetal taurine supplementation markedly stimulated postnatal growth. In sham/taurine females, fat depots, plasma free fatty acid and leptin concentrations were increased and insulin sensitivity was reduced. Insulin sensitivity was unaltered in IUGR and IUGR/taurine offspring. However, whereas IUGR offspring showed little catch-up growth, 50 % of IUGR/taurine animals displayed complete catch-up at 12 wks of age and these animals had increased fat depots and reduced insulin sensitivity. In conclusion, taurine supplementation in late gestation results in accelerated postnatal growth, which was associated with adult obesity and insulin resistance both in IUGR and normal offspring. This effect was particularly evident in females. These data suggest that foetal taurine availability is an important determinant for postnatal growth, insulin sensitivity and fat accumulation.
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| 12. |
- Karimipanah, Taghi, 1953-, et al.
(författare)
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Investigation of air quality, comfort parameters and effectiveness for two floor-level air supply systems in classrooms
- 2007
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Ingår i: Building and Environment. - : Elsevier BV. - 0360-1323 .- 1873-684X. ; 42:2, s. 647-655
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Tidskriftsartikel (refereegranskat)abstract
- The method of distributing the outdoor air in classrooms has a major impact on indoor air quality and thermal comfort of pupils. In a previous study, ([11] Karimipanah T, Sandberg M, Awbi HB. A comparative study of different air distribution systems in a classroom. In: Proceedings of Roomvent 2000, vol. II, Reading, UK, 2000. p. 1013-18; [13] Karimipanah T, Sandberg M, Awbi HB, Blomqvist C. Effectiveness of confluent jets ventilation system for classrooms. In: Idoor Air 2005, Beijing, China, 2005 (to be presented).) presented results for four and two types of air distribution systems tested in a purpose built classroom with simulated occupancy as well as computational fluid dynamics (CFD) modelling. In this paper, the same experimental setup has been used to investigate the indoor environment in the classroom using confluent jet ventilation, see also ([12] Cho YJ, Awbi HB, Karimipanah T. The characteristics of wall confluent jets for ventilated enclosures. In: Proceedings of Roomvent 2004, Coimbra, Portugal, 2004.) Measurements of air speed, air temperature and tracer gas concentrations have been carried out for different thermal conditions. In addition, 56 cases of CFD simulations have been carried to provide additional information on the indoor air quality and comfort conditions throughout the classroom, such as ventilation effectiveness, air exchange effectiveness, effect of flow rate, effect of radiation, effect of supply temperature, etc., and these are compared with measured data.
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| 13. |
- Meng, Rong, et al.
(författare)
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Online preconcentration of thyrotropin-releasing hormone (TRH) by SDS-modified reversed phase column for microbore and capillary high-performance liquid chromatography (HPLC).
- 2005
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Ingår i: Journal of chromatography. A. - : Elsevier BV. - 0021-9673. ; 1071:1-2, s. 179-84
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Tidskriftsartikel (refereegranskat)abstract
- Thyrotropin-releasing hormone (TRH, pGlu-His-Pro-amide) is an important tripeptide existing in biological systems at low concentrations. It is a fairly hydrophilic peptide, cationic in acidic solutions. Preconcentration online before reversed phase chromatography separation can enhance concentration detection limits of hydrophobic, but not hydrophilic species. The hydrophilic TRH can be preconcentrated using a reversed phase precolumn charged with sodium dodecyl sulfate (SDS). The separation also uses SDS. The preconcentration is effective for a microbore system, achieving detection limit of 250 pM for a sample size of 500 microl with electrochemical detection of the biuret complex formed post column. Preconcentration using an online precolumn is also effective in packed capillary high-performance liquid chromatography (HPLC) with a detection limit of 3 nM in 24 microl.
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| 15. |
- Persson, Mikael, 1979, et al.
(författare)
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Microglial glutamate uptake is coupled to glutathione synthesis and glutamate release.
- 2006
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Ingår i: The European journal of neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 24:4, s. 1063-70
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Tidskriftsartikel (refereegranskat)abstract
- The physiological function of microglial glutamate uptake has been debated as it is about 10% of that measured for astrocytes. This study addresses how glutamate, taken up from the extracellular space, is utilized by microglia. It was found that purified rat microglia incubated for 60 min with (3)H-glutamate had an increased intracellular accumulation of (3)H-glutamate after 12 h incubation with tumour necrosis factor alpha (TNF-alpha) but not after incubation with lipopolysaccharide (LPS). Furthermore, LPS- but not TNF-alpha-treated cells showed an increased efflux of (3)H-labelled compounds, presumably glutamate through the X(C) (-) system and treatment with LPS or TNF-alpha increased the microglial glutathione concentrations and led to an increased incorporation of (3)H-glutamate into glutathione. Depending on the stimuli, 3-6% of the total labelled contents were found in the form of glutathione and 25-35% in the form of glutamate. These results show that microglial glutamate uptake is directly coupled to glutathione synthesis and release of glutamate and/or glutamate metabolites. Additionally, the increased glutathione contents after LPS or TNF-alpha treatment were able to reduce microglial cell death after H(2)O(2) challenge, showing a potential (self)-protective function for microglial glutamate transporter expression and glutathione synthesis.
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| 16. |
- Stridh, Malin, 1979, et al.
(författare)
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Stimulated efflux of amino acids and glutathione from cultured hippocampal slices by omission of extracellular calcium: likely involvement of connexin hemichannels.
- 2008
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Ingår i: The Journal of biological chemistry. - 0021-9258. ; 283:16, s. 10347-56
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Tidskriftsartikel (refereegranskat)abstract
- Omission of extracellular Ca(2+) for 15 min from the incubation medium of cultured hippocampal slices stimulated the efflux of glutathione, phosphoethanolamine, hypotaurine, and taurine. The efflux was reduced by several blockers of gap junctions, i.e. carbenoxolone, flufenamic acid, and endothelin-1, and by the connexin43 hemichannel blocking peptide Gap26 but was unchanged by the P2X(7) receptor inhibitor oxidized ATP, a pannexin1 hemichannel blocking peptide and an inactive analogue of carbenoxolone. Pretreatment of the slices with the neurotoxin N-methyl-d -aspartate left the efflux by Ca(2+) omission unchanged, indicating that the stimulated efflux primarily originated from glia. Elevated glutamate efflux was detected when Ca(2+) omission was combined with the glutamate uptake blocker l-trans-pyrrolidine-2,4-dicarboxylate and when both Ca(2+) and Mg(2+) were omitted from the medium. Omission of Ca(2+) for 15 min alone did not induce delayed toxicity, but in combination with blocked glutamate uptake, significant cell death was observed 24 h later. Our results indicate that omission of extracellular Ca(2+) stimulates efflux of glutathione and specific amino acids including glutamate via opening of glial hemichannels. This type of efflux may have protective functions via glutathione efflux but can aggravate toxicity in situations when glutamate reuptake is impaired, such as following a stroke.
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| 17. |
- Tranberg, Mattias, 1977, et al.
(författare)
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In vitro studies on the putative function of N-acetylaspartate as an osmoregulator.
- 2007
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Ingår i: Neurochemical research. - : Springer Science and Business Media LLC. - 0364-3190 .- 1573-6903. ; 32:7, s. 1248-55
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Tidskriftsartikel (refereegranskat)abstract
- Efflux and tissue content of N-acetylaspartate (NAA) and amino acids were evaluated from cultured and acutely prepared hippocampal slices in response to changes in osmolarity. The osmoregulator taurine, but not NAA, was lost from both types of slices after moderate reductions in extracellular osmolarity (-60 mOsm) for 10-48 h. Hypoosmotic shock (-166 mOsm) for 5 min resulted in unselective efflux of several amino acids from acutely prepared slices. Notably, the efflux of taurine, but not NAA, was prominent also after the shock. Efflux of NAA was markedly enhanced by NMDA and high K(+), in particular after the stimulation period. The high K(+)-mediated efflux was decreased by high extracellular osmolarity and a NMDA-receptor antagonist. The results indicate that NAA efflux can be induced by a sudden non-physiological decrease in extracellular osmolarity but not by prolonged more moderate changes in osmolarity. The mechanisms behind the efflux of NAA by high K(+) are complex and may involve both swelling and activation of NMDA-receptors.
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| 18. |
- Tranberg, Mattias, 1977, et al.
(författare)
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N-acetylaspartate monomethyl ester increases N-acetylaspartate concentration in cultured rat hippocampal slices: effects on excitotoxicity and levels of amino acids and chloride.
- 2007
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Ingår i: Journal of neuroscience methods. - : Elsevier BV. - 0165-0270. ; 163:1, s. 105-10
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Tidskriftsartikel (refereegranskat)abstract
- N-acetylaspartate (NAA) was discovered in mammalian brain 50 years ago but its functions remain debated. One reason for the relatively slow progress of NAA research is the paucity of tools to specifically modify NAA concentrations. In this work we evaluated the use of the monomethyl ester of NAA (NAA MME) to increase the relatively low level of NAA in cultured hippocampal slices. When slices were treated with 30 mM NAA MME for 3 days the NAA concentration increased from 31.6 to 185.3 nmol/mg protein. Incubation with NAA alone increased the NAA concentration non-significantly to 65.6 nmol/mg protein. NAA MME treatment increased NAA in neurons and the increase was non-toxic as determined by the low uptake of propidium iodide, a dye that only enters damaged cells. NMDA-mediated excitotoxicity which is initiated by influx of Ca(2+) was unaltered by increased NAA levels indicating poor intracellular Ca(2+)-chelation by NAA.
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| 19. |
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| 20. |
- Wang, Xiaoyang, 1965, et al.
(författare)
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N-acetylcysteine reduces lipopolysaccharide-sensitized hypoxic-ischemic brain injury.
- 2007
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Ingår i: Annals of neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 61:3, s. 263-71
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Maternal inflammation/infection alone or in combination with birth asphyxia increases the risk for perinatal brain injury. Free radicals are implicated as major mediators of inflammation and hypoxia-ischemia (HI)-induced perinatal brain injury. This study evaluated the neuroprotective efficacy of a scavenging agent, N-acetylcysteine (NAC), in a clinically relevant model. METHODS: Lipopolysaccharide (LPS)-sensitized HI brain injury was induced in 8-day-old neonatal rats. NAC was administered in multiple doses, and brain injury was evaluated at 7 days after HI. RESULTS: NAC (200mg/kg) provided marked neuroprotection with up to 78% reduction of brain injury in the pre+post-HI treatment group and 41% in the early (0 hour) post-HI treatment group, which was much more pronounced protection than another free radical scavenger, melatonin. Protection by NAC was associated with the following factors: (1) reduced isoprostane activation and nitrotyrosine formation; (2) increased levels of the antioxidants glutathione, thioredoxin-2, and (3) inhibition of caspase-3, calpain, and caspase-1 activation. INTERPRETATION: NAC provides substantial neuroprotection against brain injury in a model that combines infection/inflammation and HI. Protection by NAC was associated with improvement of the redox state and inhibition of apoptosis, suggesting that these events play critical roles in the development of lipopolysaccharide-sensitized HI brain injury.
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| 21. |
- Welin, Anna-Karin, 1965, et al.
(författare)
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White matter injury following prolonged free radical formation in the 0.65 gestation fetal sheep brain.
- 2005
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Ingår i: Pediatric research. - 0031-3998. ; 58:1, s. 100-5
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Tidskriftsartikel (refereegranskat)abstract
- Free radicals seem to be involved in the development of cerebral white matter damage after asphyxia in the premature infant. The immature brain may be at increased risk of free radical mediated injury, as particularly the preterm infant has a relative deficiency in brain antioxidants systems, such as superoxide dismutase and glutathione peroxidase. In vitro studies show that immature oligodendrocytes express an intrinsic vulnerability to reactive oxygen species and free radical scavengers are able to protect immature oligodendrocytes from injury. The aim of this study was to examine the formation of ascorbyl radicals as a marker of oxidative stress in the preterm brain in association with cerebral white matter injury after intrauterine asphyxia. Fetal sheep at 0.65 gestation were chronically instrumented with vascular catheters and an occluder cuff around the umbilical cord. A microdialysis probe was placed in the periventricular white matter. Fetal asphyxia was induced by occlusion of the umbilical cord for 25 min (n = 10). Microdialysis samples were collected for 72 h and analyzed for ascorbyl radicals using electron spin resonance. Five instrumented fetuses served as controls. Three days after the insult, fetal brains were examined for morphologic injury. Umbilical cord occlusion resulted in prolonged and marked increase in ascorbyl radical production in the brain in connection with white matter injury, with activation of microglia cells in periventricular white matter and axonal injury. These data suggest that reperfusion injury following asphyxia in the immature brain is associated with marked free radical production.
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