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- Hultborn, Ragnar, 1946, et al.
(författare)
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Prolonged activation of soleus motoneurones following a conditioning train in soleus Ia afferents - A case for a reverberating loop?
- 1975
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Ingår i: Neuroscience letters. - 0304-3940. ; 1:3, s. 147-52
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Tidskriftsartikel (refereegranskat)abstract
- In the decerebrate cat a short train of impulses in Ia afferents from the soleus muscle (or its synergists) may cause a long latency prolonged activity in the soleus muscle as judged by EMG and tension recording. The excitability increase may stay virtually constant during long periods (several minutes) but can be terminated at any time by a train of impulses in, for example, the peroneal nerve. It is suggested that the conditioning Ia impulses activate a neuronal circuit which can maintain a reverberating activity thereby causing the heightened excitability of the soleus motoneurones.
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| 4. |
- Abbas, Abdul-Karim, 1959, et al.
(författare)
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Emetine treatment masks initial LTP without affecting long-term stability.
- 2011
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Ingår i: Brain research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 1426, s. 18-29
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Tidskriftsartikel (refereegranskat)abstract
- Applying emetine, a protein synthesis inhibitor, at 20-40μM for 90-120min prior to LTP induction in hippocampal slices from young rats (2-3weeks) and washing it out afterwards revealed a slowly developing potentiation that reached maximum after 20-30min, distinct from the LTP observed under normal conditions. Nevertheless, the later phase of this potentiation was similar to standard LTP as judged by experiments lasting up to 8h after induction. Emetine preapplication for 3h without subsequent washout resulted in a substantial decay of evoked responses. By comparison between test and control pathways, LTP could still be assessed in these experiments for up to 4-6h after induction and was found not to differ from normal, except for the slow onset. The NMDA-R blocker AP5 fully blocked LTP; however, with emetine pretreatment there was an initial depression of responses with a gradual recovery during 20-30min. This depression involved not only the field EPSP but also the presynaptic fiber volley. However, when using the protein synthesis inhibitors cycloheximide and anisomycin there was essentially no such depression. In conclusion, the present results support the idea that preexisting proteins are sufficient for inducing stable LTP. Moreover, emetine but not anisomycin or cycloheximide impairs presynaptic action potentials, leading to an apparent slow onset of LTP. The emetine-dependent effect could be due to a characteristic blocking spectrum of the drug, preferred targeting of presynaptic compartments or effects unrelated to protein synthesis.
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| 6. |
- Abbas, Abdul-Karim, 1959, et al.
(författare)
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Long-term potentiation and insult conditioning in hippocampal slices from young rats: a role for protein synthesis under chemical stress?
- 2010
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Ingår i: The 10th Biennial Meeting of the Asia-Pacific Society for Neurochemistry (APSN), October 17-20, 2010, Phuket, Thailand.
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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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| 7. |
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| 8. |
- 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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| 9. |
- Abbas, Abdul-Karim, 1959, et al.
(författare)
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Pharmacological characteristics of protein synthesis inhibitors by radioactive leucine incorporation in rat hippocampal slices: experimental evidence and pre-clinical implications
- 2011
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Ingår i: The 23rd Biennial Meeting of the International Society for Neurochemistry (ISN), August 28-September 1 2011, Athens, Greece.
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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.
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| 10. |
- 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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