1.
Abbas, Abdul-Karim, 1959, et al.
(författare)
Long-term potentiation and insult conditioning in hippocampal slices from young rats: a role for protein synthesis under chemical stress?
2010
Ingår i: The 10th Biennial Meeting of the Asia-Pacific Society for Neurochemistry (APSN), October 17-20, 2010, Phuket, Thailand.
Konferensbidrag (övrigt vetenskapligt/konstnärligt) abstract
We have previously demonstrated that in young rats (12-20-day-old) a sustained long-term potentiation (LTP) can still be induced under conditions of protein synthesis inhibition. It was therefore suggested that sufficient and necessary proteins were already available at the induction time to accomplish LTP maintenance for several hours. Against this background, we have questioned whether hippocampal slices subjected to certain insult conditions might be more sensitive to protein synthesis inhibitors. High K+ concentration has previously been reported to cause an amnesic effect in vivo as well as increasing protein turnover in vitro. We have here employed a K+ insult model under conditions when protein synthesis was inhibited. Recordings were obtained from hippocampal slices for up to 9 h, with or without a cocktail of protein synthesis inhibitors, containing cycloheximide (60 µM) and anisomycin (25 µM). High potassium (50 mM) was transiently applied (5-15 min) shortly after inducing LTP in one of two separate pathways stimulated alternatively. Additionally, an NMDA-receptor antagonist AP5 was supplied after LTP induction to minimize effects related to depolarization-induced glutamate release. Following elimination of all responses for about 30 min, both test and control responses partly recovered. The degree of remaining LTP, defined as test/control ratio, was reduced in both groups of slices (NMDA-independent depotentiation) but was significantly smaller in the drug-treated ones. We are also running an insult model based on oxidative stress, applying hydrogen peroxide (4-5 mM) before or after LTP induction; however, the results are still insufficient for a final conclusion. The potency of cycloheximide, anisomycin or cocktail of the drugs was verified by measurement of incorporation of [3H]-leucine into trichloracetic acid (TCA) precipitable macromolecules. Cycloheximide, anisomycin or cocktail, at concentrations used here caused 95%, 97% and 95% blocking effect, respectively. Our data confirm the idea that sufficient and necessary constitutive proteins are available in the young hippocampus to maintain LTP under conditions of protein synthesis inhibition. They also reveal that LTP in slices subjected to certain insult conditions early after the induction is sensitive to protein synthesis inhibition, probably due to increase in constitutive proteins turnover.
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Abbas, Abdul-Karim, 1959, et al.
(författare)
Pharmacological characteristics of protein synthesis inhibitors by radioactive leucine incorporation in rat hippocampal slices: experimental evidence and pre-clinical implications
2011
Ingår i: The 23rd Biennial Meeting of the International Society for Neurochemistry (ISN), August 28-September 1 2011, Athens, Greece.
Konferensbidrag (övrigt vetenskapligt/konstnärligt) abstract
Protein synthesis inhibitors (PSIs) constitute a major tool to validate the hypothesis of protein synthesis-dependent phase of synaptic plasticity and memory consolidation. However, several reports have showed inconsistent findings about the effect of these drugs on behavioral learning and synaptic plasticity. Testing the potencies of these drugs is hence crucial for validating such negative findings and in planning future studies. It is also necessary to examine the dose dependence, onset dynamics and reversibility, and possible effects on basal proteins. Here we used the labeled leucine as marker for the newly synthesized proteins. The fraction of leucine incorporation, following 50 min of pre-incubation, was compared between two groups of slices: a PSI-treated and a control group. Both anisomycin and cycloheximide revealed a dose-dependent but time-independent manner of inhibition reaching over 92% at concentrations well below those used in previous experiments which revealed effects on synaptic plasticity and learning. Surprisingly, washout of a “reversible” inhibitor, anisomycin was not followed by rapid reversibility of the action of the drug, the case that differs with cycloheximide. Interestingly, emetine revealed a time-dependent inhibition of protein synthesis, where levels above 80% needed drug pre-incubation for as long as 90 min. Since the duration of labeling relates to the half-life of the proteins, short-time labeling as used in this study will result in radioactivity incorporation into short-lived proteins and proteins that are synthesized in large quantities. We therefore studied the availability of newly synthesized proteins at 8-10 h following leucine incorporation. The results revealed virtually the same protein content as in slices retrieved for analysis immediately following the labeling period, indicating that the main pool of the newly synthesized proteins is of intracellular long-lived pool. This likely reflects a stable metabolic state of our prepared slices. These findings challenge current idea on the role of de novo protein synthesis in synaptic plasticity as well as brain changes underlying several neurological and psychiatric disorders.
6.
Munthe, Christian, 1962
(författare)
Etiska aspekter på regenerativ medicin : Ethical aspects on regenerative medicine
2003
Ingår i: SNIB-konferensen 2003, Chalmers tekniska högskola, Göteborg, 16-18 maj 2003.
Konferensbidrag (övrigt vetenskapligt/konstnärligt) abstract
Inom den regenerativa medicinen strävar man efter att ersätta skadat eller sjukligt biologiskt mänskligt material (celler, organ, kroppsdelar) med nya biologiska komponenter. Området aktualiserar en rad etiska frågeställningar vad gäller (1) produktionen av ersättningsmaterialet (t.ex. embryonala stamceller eller införskaffande av transplantationsvävnad från donatorer), (2) risker i samband med försök på människa (genmodifierat material, material från djur), samt (3) gränserna för hur långt man bör gå i denna slags försök att förlänga människans livsspann. Föredraget ger en kort översikt över dessa frågeställningar, ståndpunkter och argument i debatten kring dem.
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Englund Johansson, Ulrica, et al.
(författare)
In Vivo Properties of In Vitro-Propagated Neural Stem Cells After Transplantation to the Neonatal and Adult Rat Brain
2004
Ingår i: Stem Cells in the Nervous System: Functional and Clinical Implications. Research and Perspectives in Neurosciences. - Berlin, Heidelberg : Springer. - 9783642623394 - 9783642188831
Konferensbidrag (refereegranskat) abstract
The ability to isolate neural stem and precursor cells and expand them in culture has provided researchers a new tool, not only assisting studies of neural development but also providing a new source of defined and expandable cells for in vivo studies using transplantation. The purposes of this chapter are, first, to review available protocols for in vitro expansion of neural precursor cells, either epigenetically using growth factors or genetically by inserting immortalizing genes; and, second, to discuss the in vivo properties of in vitro-propagated neural stem and progenitor cells, as assessed by grafting to the developing or adult rodent brain. This discussion will focus on our own recent studies using growth factor-expanded neurosphere cells of mouse and human origin and a particularly interesting, conditionally immortalized neural cell line, RN33B.
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