Handbook of transcription factor NF-kappaB

Handbook of Transcription Factor NF-kappaB

---

Free download. Book file PDF easily for everyone and every device. You can download and read online Handbook of transcription factor NF-kappaB file PDF Book only if you are registered here. And also you can download or read online all Book PDF file that related with Handbook of transcription factor NF-kappaB book. Happy reading Handbook of transcription factor NF-kappaB Bookeveryone. Download file Free Book PDF Handbook of transcription factor NF-kappaB at Complete PDF Library. This Book have some digital formats such us :paperbook, ebook, kindle, epub, fb2 and another formats. Here is The CompletePDF Book Library. It's free to register here to get Book file PDF Handbook of transcription factor NF-kappaB Pocket Guide.

In contextual memories, an association between a positive or negative reinforcement and the contextual cues where the reinforcement occurs is formed.

The re-exposure to the context without reinforcement can lead to memory extinction or reconsolidation, depending on the number of events or duration of a single event of context re-exposure. Extinction involves the temporary waning of the previously acquired conditioned response.

1st Edition

The molecular processes underlying extinction and the mechanisms which determine if memory will reconsolidate or extinguish after retrieval are not well characterized, particularly the role of transcription factors and gene expression. These data constitutes a novel insight into the molecular mechanisms involved in the switch between memory reconsolidation and extinction.

The accurate description of the molecular mechanisms that support memory extinction is potentially useful for developing new strategies and drug candidates for therapeutic treatments of the maladaptive memory disorders such as post-traumatic stress, phobias, and drug addiction. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist. Since the original interpretation by Pavlov [1] , extinction of an associative memory was considered a new process that impedes the expression of the original association. Under this interpretation, the original memory is not abolished by extinction and, in most cases, can be recovered spontaneously or after behavioural or pharmacological treatments [2] — [5]. Such hypothesis suggests the formation of new neuronal circuits underlying the newly acquired behavioural outcome.

Several drugs, acting in a limited period after extinction induction, interfere with this process and allow the original long-term memory to be expressed [4] , [6]. The fact that protein synthesis inhibitors and NMDA-type glutamate receptors NMDAR antagonists are effective drugs affecting extinction led to the hypothesis that this process required consolidation-like mechanisms similar to the consolidation of the original memory [7] — [11]. However, beyond the requirement of de novo protein synthesis and NMDAR, some research data point out differences between the molecular mechanisms involved in memory consolidation and extinction, as the participation of protein phosphatases [12] , [13] and endocanabinoids [14].

Interestingly, both molecular mechanisms, as well as NMDAR [15] , are involved in long-term depression LTD , a neural plasticity model that induces a reversible reduction of synaptic efficacy, suggesting that synaptic weakening of the original consolidated memory trace can explain in part the neural process involved in memory extinction.

In the core of the molecular mechanisms involved in the long-term persistence of memory trace is the regulation of gene expression, conducted via the activation of specific transcription factors TFs. These mechanisms are considered key molecular processes in consolidation [16] — [18] and reconsolidation [19] — [22]. Related to the role of gene transcription during LTM extinction there is indirect evidences provided by the use of in vivo protein synthesis inhibition and the inhibition of protein kinases that are involved in gene regulation.

At our knowledge, only two reports evaluate the hypothesis by direct blockade of the transcriptional machinery [23] , [24]. One of these reports studied the effect of intrahippocampal injection of the transcription inhibitors alpha-amanitin and DRB on inhibitory avoidance in rats [23]. In that report, the drug infusions impaired memory extinction when administered before the extinction protocol, suggesting that the transcriptional activity is required for consolidation of extinction.

Conversely, Lin and colleagues reported that memory extinction is insensitive to actinomycin-D and depends upon calcineurin activity that induces dephosphorylation of cAMP response element binding protein CREB [24]. This last finding suggests that CREB inhibition by calcineurin and the consequent gene transcription inhibition could be part of the molecular mechanisms involved in extinction. In the context-signal memory in crabs [25] , the presentation of a danger stimulus an opaque screen passing over the animal provokes an escape response that is actively replaced in successive events by a freezing response as a consequence of the repetition of the stimulation [26].

This context-dependent memory is defined at testing as a significantly lower response to the danger stimulus by a trained group of animals than by an untrained control group. Animals with fully consolidated LTM that are exposed to the training context would either reconsolidate or extinguish LTM depending on the length of the context exposure session [10]. Crab's LTM extinction is blocked by protein synthesis inhibitors [10].

Such activation was found in different types of contextual memory models as context-signal memory in the crab Chasmagnathus [21] , contextual fear conditioning in rats [34] and inhibitory avoidance in mice [22]. Conversely, 2 h re-exposure to the context induces protein synthesis-dependent extinction [10].

This extinction is expressed during testing session as a lack of retention, in spite of the strong training protocol used during the training day. Under such conditions, a long-term association between context features and the danger stimulus is formed [35].

Nuclear factor NF-kappa-B p105 subunit

This association is assessed as a significant lower level of response of TR group respect to CT group at testing. Such a low level is an expression of an active change from escape to freezing response [36]. Twenty four h later, the animals were injected in the pericardial sac with 6. This result confirms previous results showing that sulfasalazine has no effect administered 24 h after training without re-exposure to the training context. Conversely, no memory retention was found for the two trained groups that were injected with vehicle or sulfasalazine and then re-exposed to the training context no significant differences between CT and TR pair of groups, Figure 1b.

These results indicate memory extinction for both groups re-exposed to the training context for 2 h. Effect of sulfasalazine injection 24 h after training without re-exposure session. Left panel : Experimental design. On day 1 the animals were trained with 15 trials TR groups or were located in the training apparatus but remained untrained CT groups.

Right graph: Performance at testing session. Effect of sulfasalazine 20 min before prolonged re-exposure session. Left panel : On day 1 the animals were trained with 15 trials TR groups or were located in the actometers but remained untrained CT groups. Effect of sulfasalazine in spontaneous recovery. Left panel : the same as in B, but the testing session was given 48 h after the extinction protocol. In the crab model, spontaneous recovery of memory retention occurs between 2 and 3 days after extinction induction Hepp Y, Pedreira ME, personal communication.

In order to study the effect of sulfasalazine on spontaneous recovery of extinction, we performed the following experiment with the same design of the previous one but with 48 h interval between extinction session and testing, instead of 24 h Figure 1c , left diagram. Although the results of the previous experiment are in agreement with extinction facilitation, the lack of retention in sulfasalazine-injected group can also be explained in terms of impairment of the original memory trace induced during memory reactivation by retrieval. As shown in the previous section, sulfasalazine does not impair memory when injected 24 h after training without context re-exposure but shows amnesic effect if it is administered prior to 5 min context re-exposure.

Thus, in the last experiment Fig 1c memory may become labile after retrieval induced by context re-exposure.

NF-kappaB p65 elisa kit | Rat NF-kappaB p65 ELISA Kit-NP_

However, in previous studies on this model, Pedreira and Maldonado demonstrated, using cycloheximide, that the original memory remained unaffected after a long re-exposure of 1 or 2 h, i. In that circumstance, extinction was impeded by protein synthesis inhibition [10].

Those findings supported the idea that reconsolidation and extinction are not coexisting, so that the original memory cannot be disrupted by drugs when an extinction process is ongoing. We performed the following experiments in order to evaluate these two alternative interpretations for sulfasalazine effect: extinction facilitation or original memory impairment.

In previous studies on this model, context re-exposure of 2 h failed to induce extinction when the danger stimulus was presented at the end of the extinction session, before animals are removed from the training context [28]. This finding prompted us to the following proposition: If sulfasalazine injection disrupts the original memory, no retention should be found even after a stimulus presentation at the end of the 2 h re-exposure session. Taking advantage of this tool, it could be possible to dissect lack of retention due to extinction facilitation from that due to original memory impairment.

Thus, in the following experiment the same design was used but we included one stimulus presentation at the end of the extinction session Fig 2a.

As expected on the basis of previous studies [28] , we found that the stimulus presentation impeded short-term and long-term extinction in the TR-Veh group Figure 2b and c CT-Veh vs. Thus, these findings suggest that the original memory was not affected by sulfasalazine administration prior to extinction session. Experimental design: On day 1 the animals were trained with 15 trials TR groups or were located in the training apparatus but remained untrained CT groups.

At the end of the 2h context re-exposure one trial was presented. Performance elicited by the trial at the end of the extinction session.

Recommended for you

Performance at testing session. In order to obtain further evidence, we performed an experiment in which an extinction session is presented 24 h after training and the testing session was delayed from 48 h to 72 h Figure 3a , upper diagram. A delay in the spontaneous recovery of the original memory may be expected if sulfasalazine induces extinction facilitation. However, for longer periods between extinction session and testing the original memory should be recovered.

As expected, the analysis of the Veh pair of groups showed memory recovery CT-Veh vs. Thus, sulfasalazine impedes memory recovery even 72 h after the extinction session. In the third experiment of this section we explored if it is possible to induce the recovery of the original memory by means of reinstatement [2] , [37] in SSZ treated animals. For this purpose, we introduced a session of 5 danger stimulus presentations in a different context context B 48 h after the extinction session and 1 day before testing performed in the normal context context A Figure 4a left panel.

Figure 4a shows memory recovery in the Veh pair of groups CT-Veh vs. The reinstatement with 5 trials fails to reveal the original memory over sulfasalazine-facilitated memory extinction. Left panel: Experimental design. The reinstatement with 10 trials reveals the original memory over sulfasalazine-facilitated memory extinction. Left panel: Experimental designs in A but using 10 trials during the reinstatement session. On day 1 the animals were trained with 10 trials TR groups or were located in the context B but remained untrained CT groups.

Plain box: context A. Stripped box: context B.

Next, we repeated the previous experiment but including 10 trials instead of 5 of reinstatement Figure 4b , left panel. As shown in the graph of Figure 4b , the stronger reinstatement session was able to recover memory retention in both Veh and SSZ pairs of groups CT-Veh vs.

Finally, in order to rule out the possibility that 10 trials in a different context are able to induce long-term memory retention per se , we included an experiment in which a group of animals was trained in context B with 10 trials and the other group was exposed to context B but remained untrained. The following day, animals were tested in context A and no statistically significant differences were found between groups Fig 4c , left panel , indicating that 10 trials were not enough to induce significant retention. This result is expected taken into account that 15 trials, but not 10 trials, are required to induce long-term memory in this model [27] , and that this memory is context-specific [35] , [38].

Thus, the retention found in the previous experiment was due to memory reinstatement from extinction, indicating the presence of the original memory.

Authors affiliations

The experiments of the present section support that the retention deficit induced by sulfasalazine is due to extinction facilitation and not to impairment of the original memory. For this purpose nuclear extracts were obtained from the central brain at different time points during extinction session. In the first experiment, TR group received a 15 trials training and CT group remained in the training chamber without stimulation.

Twenty four h later, each group was divided in three groups of 20 crabs that were re-exposed to the training context and remained there either for 5, 45 or min. Animals were then anesthetized in ice-cold water, sacrifice, and the central brain was dissected Fig 5a. Using this probe one retarded band is observed. These time points are coincident with the induction of memory extinction [10]. Top diagram: experimental design.

Nuclear factor NF-kappa-B p105 subunit

On day two, the CT-TR groups were re-exposed to the training context. At different time points indicated by arrows , animals of CT and TR pair of groups were anesthetized and nuclear extracts from the 20 central brains of each group were obtained. The specific band is indicated with a filled arrow.

• Reading Television (New Accents (Routledge (Firm)).)
• Heterosexual Masculinities: Contemporary Perspectives from Psychoanalytic Gender Theory
• A Thousand Sighs, A Thousand Revolts: Journeys in Kurdistan
• The Morality of Happiness
• The Power of Strategic Commitment: Achieving Extraordinary Results Through Total Alignment and Engagement