| 1. |
- 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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| 2. |
- Huang, Fen-Sheng, 1961, et al.
(författare)
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Bidirectional synaptic plasticity in response to single or paired pulse activation of NMDA receptors.
- 2010
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Ingår i: Neuroscience research. - : Elsevier BV. - 1872-8111 .- 0168-0102. ; 67:2, s. 108-116
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Tidskriftsartikel (refereegranskat)abstract
- It is still incompletely known how NMDA receptors (NMDA-R) regulate bidirectional synaptic plasticity. We examined this issue by an experimental protocol in which paired pulse stimulation (PPS) with 50ms interstimulus interval and basal frequency of 0.1Hz was applied to CA1 area of rat hippocampal slices during low Mg(2+) perfusion. Under blockade of NMDA-Rs by AP5, PPS for 12-60min led to only a minor depression. In contrast, when PPS was applied in the absence of AP5, there was a prominent short-term potentiation (STP), mainly of AMPA-R mediated responses, with peak at 1min and lasting 10-15min. The STP was followed by a slowly developing long-term depression (LTD). Applying AP5 during the STP, converted it to a stable increase relative to the control pathway. Following peak STP, plasticity was controlled in a composite manner. Whereas the initial decay was counteracted by NMDA-R activation, the following LTD was dependent on such activation. Our data suggest that synaptic changes do not only depend on the instantaneous, NMDA-dependent Ca(2+) concentration in the dendritic spine, but are also influenced by prior induction events. In addition to NMDA-R driven processes, passive relaxation contributes to the synaptic plasticity and in some cases outbalances the active control.
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| 3. |
- Li, Rui, 1975, et al.
(författare)
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Reduced anti-contractile effect of perivascular adipose tissue on mesenteric small arteries from spontaneously hypertensive rats: Role of Kv7 channels
- 2013
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999. ; 698:1-3, s. 310-315
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Tidskriftsartikel (refereegranskat)abstract
- Perivascular adipose tissue (PVAT) has been shown to produce vasoactive substances and regulate vascular tone. This function of PVAT has been reported to be altered in hypertension. However, the underlying mechanisms are not fully understood. In this study we used age-matched normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) as well as Sprague-Dawley rats and tested effects of PVAT on mesenteric small arteries. Vessels were mounted in a Mulvany-Halpern myograph and cumulative concentration-response relations to noradrenaline were determined in the presence or absence of PVAT. We found that PVAT has an anti-contractile effect on mesenteric small vessels, irrespective of strains. A reduced effect of PVAT was observed in SHR compared to WKY rats; the difference between strains was eliminated by 10 mu M XE991, a blocker of Kv7 (KCNQ) voltage-dependent potassium channels. The anti-contractile effect of PVAT was not affected by depolarizing smooth muscle cells with high K+ solution. Sensitivities to exogenous vasodilators acetylcholine or sodium nitroprusside were not potentiated but reduced in vessels with PVAT. Our results suggest that the reduced anti-contractile effect of PVAT in SHR correlates with a deficiency in Kv7 channels. Diffusion hindrance of PVAT is also a factor that should be considered in investigations on rat mesenteric small arteries. (c) 2012 Elsevier B.V. All rights reserved.
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