scholarly journals Long-Lasting Effects of GABA Infusion Into the Cerebral Cortex of the Rat

2000 ◽  
Vol 7 (1-2) ◽  
pp. 1-8 ◽  
Author(s):  
Teresa Montiel ◽  
Daniel Almeida ◽  
Iván Arango ◽  
Eduardo Calixto ◽  
César Casasola ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Long Term Potentiation ◽  
Information Storage ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Receptor Stimulation ◽  
Paroxysmal Activity ◽  
The Brain

In electrophysiological terms, experimental models of durable information storage in the brain include long-term potentiation (LTP), long-term depression, and kindling. Protein synthesis correlates with these enduring processes. We propose a fourth example of long-lasting information storage in the brain, which we call the GABA-withdrawal syndrome (GWS). In rats, withdrawal of a chronic intracortical infusion of GABA, a ubiquitous inhibitory neurotransmitter, induced epileptogenesis at the infusion site. This overt GWS lasted for days. Anisomycin, a protein synthesis inhibitor, prevented the appearance of GWSin vivo. Hippocampal and neocortical slices showed a similar post-GABA hyperexcitabilityin vitroand an enhanced susceptibility to LTP induction. One to four months after the epileptic behavior disappeared, systemic administration of a subconvulsant dose of pentylenetetrazol produced the reappearance of paroxysmal activity. The long-lasting effects of tonicGABAAreceptor stimulation may be involved in long-term information storage processes at the cortical level, whereas the cessation ofGABAAreceptor stimulation may be involved in chronic pathological conditions, such as epilepsy. Furthermore, we propose that GWS may represent a common key factor in the addiction to GABAergic agents (for example, barbiturates, benzodiazepines, and ethanol). GWS represents a novel form of neurono-glial plasticity. The mechanisms of this phenomenon remain to be understood.

Ischemic tolerance in the rat neocortex following hypothermic preconditioning

2000 ◽  
Vol 93 (5) ◽  
pp. 845-851 ◽  
Author(s):  
Shinsaku Nishio ◽  
Masatoshi Yunoki ◽  
Zong-Fu Chen ◽  
Matthew J. Anzivino ◽  
Kevin S. Lee
Keyword(s):  
Protein Synthesis ◽  
Cerebral Infarction ◽  
Ischemic Tolerance ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Content Type ◽  
Series Of Experiments ◽  
The Brain ◽  
Fine Print

Object. Ischemic neuronal damage associated with neurological and other types of surgery can have severe consequences for functional recovery after surgery. Hypothermia administered during and/or after ischemia has proved to be clinically beneficial and its effects often rival or exceed those of other therapeutic strategies. In the present study the authors examined whether transient hypothermia is an effective preconditioning stimulus for inducing ischemic tolerance in the brain.Methods. Adult rats were subjected to a 20-minute period of hypothermic preconditioning followed by an interval ranging from 6 hours to 7 days. At the end of this interval, the animals were subjected to transient focal ischemia induced by clamping one middle cerebral artery and both carotid arteries for 1 hour. The volume of cerebral infarction was assessed 1 or 7 days postischemia. In the first series of experiments, hypothermic preconditioning (28.5°C) with a postconditioning interval of 1 day reduced the extent of cerebral infarction measured 1 and 7 days postischemia. In the second series, hypothermic preconditioning (31.5°C) with postconditioning intervals of 6 hours, 1 day, or 2 days (but not 7 days) reduced the extent of cerebral infarction measured 1 day postischemia. Treatment with the protein synthesis inhibitor anisomycin blocked the protective effect of hypothermic preconditioning. In a final series of experiments, in vitro brain slices prepared from hypothermia-preconditioned (nonischemic) animals were shown to tolerate a hypoxic challenge better than slices prepared from unconditioned animals.Conclusions. These findings indicate that hypothermic preconditioning induces a form of delayed tolerance to focal ischemic damage. The time course over which tolerance occurs and the ability of a protein synthesis inhibitor to block tolerance suggest that increased expression of one or more gene products is necessary to establish tissue tolerance following hypothermia. The attenuation of hypoxic injury in vitro following in vivo preconditioning indicates that tolerance is due, at least in part, to direct effects on the brain neuropil. Hypothermic preconditioning could provide a relatively low-risk approach for improving surgical outcome after invasive surgery, including high-risk neurological and cardiovascular procedures.

Corticotropin-Releasing Factor Produces a Protein Synthesis–Dependent Long-Lasting Potentiation in Dentate Gyrus Neurons

2000 ◽  
Vol 83 (1) ◽  
pp. 343-349 ◽  
Author(s):  
Hai L. Wang ◽  
Li Y. Tsai ◽  
Eminy H. Y. Lee
Keyword(s):  
Protein Synthesis ◽  
Synaptic Transmission ◽  
Dentate Gyrus ◽  
Late Phase ◽  
Long Term Potentiation ◽  
Corticotropin Releasing Factor ◽  
Rat Hippocampus ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor

Corticotropin-releasing factor (CRF) was shown to produce a long-lasting potentiation of synaptic efficacy in dentate gyrus neurons of the rat hippocampus in vivo. This potentiation was shown to share some similarities with tetanization-induced long-term potentiation (LTP). In the present study, we further examined the mechanism underlying CRF-induced long-lasting potentiation in rat hippocampus in vivo. Results indicated that the RNA synthesis inhibitor actinomycin-D, at a concentration that did not change basal synaptic transmission alone (5 μg), significantly decreased CRF-induced potentiation. Similarly, the protein synthesis inhibitor emetine, at a concentration that did not affect hippocampal synaptic transmission alone (5 μg), also markedly inhibited CRF-induced potentiation. These results suggest that like the late phase of LTP, CRF-induced long-lasting potentiation also critically depend on protein synthesis. Further, prior maximum excitation of dentate gyrus neurons with tetanization occluded further potentiation of these neurons produced by CRF and vise versa. Moreover, quantitative reverse transcription-polymerase chain reaction analysis revealed that CRF mRNA level in the dentate gyrus was significantly increased 1 h after LTP recording. Together with our previous findings that CRF antagonist dose-dependently diminishes tetanization-induced LTP, these results suggest that both CRF-induced long-lasting potentiation and tetanization-induced LTP require protein synthesis and that CRF neurons are possibly involved in the neural circuits underlying LTP.

Evidence for a role of phospholipase A2 in the mechanism of LHRH priming in rat anterior pituitary tissue

1994 ◽  
Vol 141 (1) ◽  
pp. 15-31 ◽  
Author(s):  
F J Thomson ◽  
M S Johnson ◽  
R Mitchell ◽  
B Wolbers
Keyword(s):  
Protein Synthesis ◽  
Anterior Pituitary ◽  
Priming Effect ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Pituitary Tissue ◽  
Gonadotrophin Secretion ◽  
Lh Release ◽  
Functional Relevance

Abstract The phospholipase A2 (PLA2) inhibitors, quinacrine, p-bromophenacyl bromide, ONO-RS-082, aristolochic acid and chloracysine blocked the priming effect of LHRH, but not acute LHRH-induced gonadotrophin release measured in anterior pituitary pieces in pro-oestrous rats in vitro. These results suggest that the intracellular mechanisms underlying LHRH priming are distinct from those which mediate LH release in the present circumstances in that they involve PLA2. Furthermore, neither LHRH-induced LH release from preprimed tissue nor Ca2+-induced LH release were attenuated by quinacrine, indicating that this inhibitor does not interfere with the general Ca2+-dependent secretory apparatus of the gonadotroph and that the critical period for its action is in the induction of priming. LHRH induced the release of [3H]arachidonic acid ([3H]AA) from [3H]AA-prelabelled anterior pituitary tissue from pro-oestrous rats; a response which was sensitive to inhibitors of PLA2, of protein kinase C (PKC) and of protein synthesis. Activation of PKC also resulted in [3H]AA release which was inhibited with exactly the same pharmacological profile as the response to LHRH. Both gonadotrophin secretion and [3H]AA release responses to LHRH and to phorbol ester varied in parallel during the oestrous cycle and in ovariectomized/oestradiol-17β-replaced animals, as did their sensitivity to quinacrine and the protein synthesis inhibitor cycloheximide. These results indicate that LHRH priming is dependent on a hormonally regulated cascade involving a distinct form of PKC acting through a protein synthesis-dependent step to release AA by means of PLA2 activity. The priming effect was mimicked (at least in part) by conditioning preincubation with AA, confirming the functional relevance of this signalling cascade. Results using standard inhibitors of lipoxygenase/epoxygenase pathways were equivocal as to whether these pathways were critically involved, whilst cyclo-oxygenase inhibitors were completely without effect. The steps downstream from AA (and its possible metabolites) by which stimulus–secretion coupling is up-regulated in priming remain to be clarified. Journal of Endocrinology (1994) 141, 15–31

Drug inhibition of memory formation in chickens II. Short-term memory

1971 ◽  
Vol 178 (1053) ◽  
pp. 455-464 ◽  
Keyword(s):  
Protein Synthesis ◽  
Sodium Pump ◽  
Short Term Memory ◽  
Memory Loss ◽  
Protein Synthesis Inhibitor ◽  
Protein Synthesis Inhibitors ◽  
Short Term ◽  
Synthesis Inhibitor ◽  
Term Memory

1. Memory in day-old-chickens during the first few hours after learning can be made to decline by the prior intracranial injection of two classes of drugs. 2. Sodium pump inhibitors in increasing doses cause increasingly rapid loss of memory. 3. Protein synthesis inhibitors in increasing doses attain a maximum potency in causing memory decline and the rate may not be further accelerated by higher doses. 4. Adding a sodium pump inhibitor to the inhibition of protein synthesis increases memory loss. 5. Adding a protein synthesis inhibitor to a sodium pump inhibitor causes no further loss. 6. Therefore within a few minutes of learning a short-term memory of limited time span but independent of protein synthesis becomes supplemented and eventually replaced by a long-term storage requiring protein synthesis. The amount of long-term store is set by the amount of short-term memory. 7. The short-term store could be directly dependent on post-activation enhancement of Na + extrusion from neurons. Some physiological mechanisms by which this could be achieved and how this might activate protein synthesis are discussed.

Temporal phases of long-term potentiation (LTP): myth or fact?

2015 ◽  
Vol 26 (5) ◽  
pp. 507-546 ◽  
Author(s):  
Abdul-Karim Abbas ◽  
Agnès Villers ◽  
Laurence Ris
Keyword(s):  
Protein Synthesis ◽  
De Novo ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Long Term Memory ◽  
Protein Synthesis Inhibitor ◽  
Protein Synthesis Inhibitors ◽  
Early Protein ◽  
Term Potentiation

AbstractLong-term potentiation (LTP) remains the most widely accepted model for learning and memory. In accordance with this belief, the temporal differentiation of LTP into early and late phases is accepted as reflecting the differentiation of short-term and long-term memory. Moreover, during the past 30 years, protein synthesis inhibitors have been used to separate the early, protein synthesis-independent (E-LTP) phase and the late, protein synthesis-dependent (L-LTP) phase. However, the role of these proteins has not been formally identified. Additionally, several reports failed to show an effect of protein synthesis inhibitors on LTP. In this review, a detailed analysis of extensive behavioral and electrophysiological data reveals that the presumed correspondence of LTP temporal phases to memory phases is neither experimentally nor theoretically consistent. Moreover, an overview of the time courses of E-LTP in hippocampal slices reveals a wide variability ranging from <1 h to more than 5 h. The existence of all these conflictual findings should lead to a new vision of LTP. We believe that the E-LTP vs. L-LTP distinction, established with protein synthesis inhibitor studies, reflects a false dichotomy. We suggest that the duration of LTP and its dependency on protein synthesis are related to the availability of a set of proteins at synapses and not to the de novo synthesis of plasticity-related proteins. This availability is determined by protein turnover kinetics, which is regulated by previous and ongoing electrical activities and by energy store availability.

scholarly journals Different Training Procedures Recruit Either One or Two Critical Periods for Contextual Memory Consolidation, Each of Which Requires Protein Synthesis and PKA

1998 ◽  
Vol 5 (4) ◽  
pp. 365-374 ◽  
Author(s):  
Roussoudan Bourtchouladze ◽  
Ted Abel ◽  
Nathaniel Berman ◽  
Rachael Gordon ◽  
Kyle Lapidus ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Time Course ◽  
Contextual Fear Conditioning ◽  
Long Term Memory ◽  
Protein Synthesis Inhibitor ◽  
Critical Periods ◽  
Synthesis Inhibitor ◽  
Contextual Memory ◽  
Contextual Fear

We have used a combined genetic and pharmacological approach to define the time course of the requirement for protein kinase A (PKA) and protein synthesis in long-term memory for contextual fear conditioning in mice. The time course of amnesia in transgenic mice that express R(AB) and have genetically reduced PKA activity in the hippocampus parallels that observed both in mice treated with inhibitors of PKA and mice treated with inhibitors of protein synthesis. This PKA- and protein synthesis-dependent memory develops between 1 hr and 3 hr after training. By injecting the protein synthesis inhibitor anisomycin or the PKA inhibitor Rp-cAMPs at various times after training, we find that depending on the nature of training, contextual memory has either one or two brief consolidation periods requiring synthesis of new proteins, and each of these also requires PKA. Weak training shows two time periods of sensitivity to inhibitors of protein synthesis and PKA, whereas stronger training exhibits only one. These studies underscore the parallel dependence of long-term contextual memory on protein synthesis and PKA and suggest that different training protocols may recruit a common signaling pathway in distinct ways.

146 EFFECT OF PROTEIN SYNTHESIS INHIBITOR ON BOAR SPERM CAPACITATION AND FERTILIZATION IN VITRO

2014 ◽  
Vol 26 (1) ◽  
pp. 186
Author(s):  
Y. Okudaira ◽  
H. Funahashi
Keyword(s):  
Protein Synthesis ◽  
Acrosome Reaction ◽  
Specific Inhibitor ◽  
Protein Synthesis Inhibitor ◽  
Sperm Viability ◽  
Sperm Capacitation ◽  
Synthesis Inhibitor ◽  
Mitochondrial Ribosome ◽  
Cytoplasmic Ribosome

In human, bovine, mouse, and rat sperm, translation of RNA to proteins in the mitochondrial ribosome during capacitation has been reported to be important for fertilization. The objective of this study was to examine effect of protein synthesis inhibitor (ribosome inhibitor) on boar sperm capacitation and IVF. Sperm from an ejaculated sperm-rich fraction of Berkshire boars were washed by centrifugation (1500 rpm for 35 min) in a Percoll gradient (45/90%) and then incubated in modified Medium-199 containing 0.4% BSA and 5 mM caffeine sodium benzoate, supplemented with or without a mitochondrial ribosome-specific (55S ribosome) inhibitor, chloramphenicol (CP; 0.3 mM), or a cytoplasmic ribosome-specific (80S ribosome) inhibitor, cyclohexide (CH; 3.6 mM), in an atmosphere of 5% CO2 in air at 39°C for 45 or 90 min. At 45 and 90 min after culture, sperm viability, motility, and chlortetracyclin-stained patterns (to assess the sperm functional status, capacitation, and acrosome reaction) were examined. Porcine oocytes were matured in vitro for 44 h in porcine oocyte medium supplemented with eCG, hCG, and dibutyryl cyclic adenosine monophosphate for the first 20 h. Matured oocytes after the removal of cumulus cells were co-cultured with sperm (final conc.: 2.5 × 105 cells mL–1) in the absence or presence of CP or CH for 8 h. Sperm penetrability was also determined. Statistical analyses of data from 4 replicated trials were performed by ANOVA. After 45 and 90 min of culture, neither CP nor CH affected sperm viability and motility (P > 0.05). The addition of CP after 45 and 90 min of culture significantly (P < 0.05) decreased capacitated and acrosome-reacted sperm rates, as detected by chlortetracyclin fluorescence assay (capacitated: control 9.6 v. CP 5.6%, control 17.8 v. CP 10.2%; acrosome reacted: control 4.6 v. CP 2.2%, control 9.2 v. CP 4.8%, respectively; P < 0.05). In the presence of CH, IVF rate and number of sperm per penetrated egg were decreased (control 80.8 v. CH 46.8%, 2.2 v. 1.4, respectively; P < 0.05). In the presence of CH, however, the percentage of metaphase II oocytes after co-culture with sperm for 8 h was lower than other 2 groups (control 87.6 v. CP 85.5 v. CH 74.0%; P < 0.05), and the percentage of A/T-II oocytes was higher than in the other 2 groups (control 1.1 v. CP 0 v. CH 9.4%; P < 0.05). From these results, we conclude that mitochondrial ribosome-specific inhibitor, chloramphenicol, affects capacitation and acrosome reaction but not penetration, whereas cytoplasmic ribosome-specific inhibitor, cyclohexide, decreases the number of oocytes that reach metaphase II stage and are penetrated.

Role of corticosterone in TNF and IL-6 production in isolated perfused rat liver

1995 ◽  
Vol 268 (3) ◽  
pp. R699-R706 ◽  
Author(s):  
J. Liao ◽  
J. A. Keiser ◽  
W. E. Scales ◽  
S. L. Kunkel ◽  
M. J. Kluger
Keyword(s):  
Protein Synthesis ◽  
Rat Liver ◽  
Intravenous Infusion ◽  
Isolated Perfused Rat Liver ◽  
Protein Synthesis Inhibitor ◽  
Perfused Rat Liver ◽  
Synthesis Inhibitor ◽  
In Situ Data ◽  
Data Support

Using an isolated perfused rat liver (IPRL) preparation, we assessed whether corticosterone may contribute to the rise in tumor necrosis factor (TNF) and interleukin-6 (IL-6) in rats after injection with lipopolysaccharide (LPS) or exposure to psychological stress. Intravenous infusion of LPS into the IPRL led to dose-dependent increases in TNF and IL-6 concentrations in the effluent. Anisomycin, a protein synthesis inhibitor, completely blocked the rise in TNF and IL-6 concentration in the IPRL effluent, supporting the hypothesis that the synthesis (or release) of these cytokines was dependent on protein synthesis. Intravenous infusion of corticosterone at nonstressed (35 ng/ml) and stressed levels (350 ng/ml) increased TNF and/or IL-6 release. However, when LPS was combined with corticosterone, the lower dose of corticosterone facilitated the release of cytokines, whereas the higher dose of corticosterone suppressed the release of cytokines. We then showed that isolated Kupffer cells were capable of significant TNF and IL-6 production and that corticosterone decreased LPS-induced cytokine production in these cells. Our data support the hypothesis that the liver is an important source of circulating cytokines in response to LPS. In addition, although in vitro data generally support the hypothesis that corticosterone suppresses the production of cytokines, our in situ data support the hypothesis that physiological levels of corticosterone cause an increase in TNF and IL-6.

scholarly journals TePhe, a tellurium-containing phenylalanine mimic, allows monitoring of protein synthesis in vivo with mass cytometry

2019 ◽  
Vol 116 (17) ◽  
pp. 8155-8160 ◽  
Author(s):  
Jay Bassan ◽  
Lisa M. Willis ◽  
Ravi N. Vellanki ◽  
Alan Nguyen ◽  
Landon J. Edgar ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Direct Detection ◽  
Aromatic Amino Acids ◽  
Protein Synthesis Inhibitor ◽  
Mass Cytometry ◽  
Synthesis Inhibitor ◽  
Molecular Specificity ◽  
Noncanonical Amino Acid

Protein synthesis is central to maintaining cellular homeostasis and its study is critical to understanding the function and dysfunction of eukaryotic systems. Here we report L-2-tellurienylalanine (TePhe) as a noncanonical amino acid for direct measurement of protein synthesis. TePhe is synthetically accessible, nontoxic, stable under biological conditions, and the tellurium atom allows its direct detection with mass cytometry, without postexperiment labeling. TePhe labeling is competitive with phenylalanine but not other large and aromatic amino acids, demonstrating its molecular specificity as a phenylalanine mimic; labeling is also abrogated in vitro and in vivo by the protein synthesis inhibitor cycloheximide, validating TePhe as a translation reporter. In vivo, imaging mass cytometry with TePhe visualizes translation dynamics in the mouse gut, brain, and tumor. The strong performance of TePhe as a probe for protein synthesis, coupled with the operational simplicity of its use, suggests TePhe could become a broadly applied molecule for measuring translation in vitro and in vivo.

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