scholarly journals Transcription of a plasticity gene is activated by neuronal hyperpolarization

2019 ◽  
Author(s):  
Zhonghua Zhu ◽  
Tamara Sanchez Ortiz ◽  
Shaul Mezan ◽  
Sebastian Kadener ◽  
Justin Blau
Keyword(s):  
Transcription Factor ◽  
Synaptic Plasticity ◽  
Neuronal Activity ◽  
Mushroom Body ◽  
Transcriptional Factors ◽  
List Type ◽  
Circadian Pacemaker ◽  
Pacemaker Neurons ◽  
Rhythmic Expression

SummaryLong term synaptic plasticity requires transcription in response to changes in neuronal activity. While genes induced by neuronal activity have been extensively studied, genes induced by hyperpolarization are largely unknown. We focused on Pura, a Rho1 GEF whose rhythmic expression drives the daily retraction of the projections of Drosophila LNv circadian pacemaker neurons. We found that Pura transcription is repressed by activity and induced by hyperpolarization in LNvs – the opposite of typical activity-regulated genes. Pura is repressed by activity-regulated transcriptional factors including Mef2 and Sr (fly Egr-1) and activated by Toy, a Pax6 transcription factor. toy transcription is also induced by inactivity. Thus toy and Pura represent a class of genes induced by hyperpolarization.HighlightsHyperpolarization activates transcription of Pura, a plasticity geneThis phenomenon occurs in circadian pacemaker neurons and mushroom body neuronsThe Pura enhancer integrates recent neuronal activity to regulate transcriptionHyperpolarization activates transcription of toy (Pax-6), which then activates Pura

scholarly journals Suppression of CHOP Reduces Neuronal Apoptosis and Rescues Cognitive Impairment Induced by Intermittent Hypoxia by Inhibiting Bax and Bak Activation

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Linhao Xu ◽  
Yanli Bi ◽  
Yizhou Xu ◽  
Yihao Wu ◽  
Xiaoxue Du ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Synaptic Plasticity ◽  
Signaling Pathway ◽  
Intermittent Hypoxia ◽  
Specific Chemical ◽  
Activating Transcription Factor ◽  
Induced Apoptosis

Our previous study showed that growth arrest- and DNA damage-inducible gene 153 (GAD153/CHOP) plays an important role in intermittent hypoxia- (IH-) induced apoptosis and impaired synaptic plasticity. This study is aimed at determining which signaling pathway is activated to induce CHOP and the role of this protein in mitochondria-dependent apoptosis induced by IH. In the in vivo study, mice were placed in IH chambers for 8 h daily over a period of 2 weeks; the IH chambers had oxygen (O2) concentrations that oscillated between 10% and 21%, cycling every 90 s. In the in vitro study, PC12 cells were exposed to 21% O2 (normoxia) or 8 IH cycles (25 min at 21% O2 and 35 min at 0.1% O2 for each cycle). After 2 weeks of IH treatment, we observed that the expression levels of phosphorylated protein kinase-like endoplasmic reticulum kinase (p-PERK), activating transcription factor 4 (ATF-4) and phosphorylated eukaryotic initiation factor 2 alpha (p-elf2α), were increased, but the levels of activating transcription factor 6 (ATF-6) and inositol-requiring enzyme 1 (IRE-1) were not increased. GSK2606414, a specific chemical inhibitor of the PERK pathway, reduced the expression of p-PERK, ATF-4, p-elf2α, and CHOP and rescued ER structure. In addition, Bax and Bak accumulated in the mitochondria after IH treatment, which induced cytochrome c release and initiated apoptosis. These effects were prevented by GSK2606414 and CHOP shRNA. Finally, the impaired long-term potentiation and long-term spatial memory in the IH group were rescued by GSK2606414. Together, the data from the in vitro and in vivo experiments indicate that IH-induced apoptosis and impaired synaptic plasticity were mediated by the PERK-ATF-4-CHOP pathway. Suppressing PERK-ATF-4-CHOP signaling pathway attenuated mitochondria-dependent apoptosis by reducing the expression of Bax and Bak in mitochondria, which may serve as novel adjunct therapeutic strategy for ameliorating obstructive sleep apnea- (OSA-) induced neurocognitive impairment.

scholarly journals Thinking through acidic Ca2+ stores

2018 ◽  
Vol 11 (558) ◽  
pp. eaau3342
Author(s):  
Sandip Patel ◽  
Eugen Brailoiu
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Metabotropic Glutamate Receptors ◽  
Long Term Potentiation ◽  
Glutamate Signaling ◽  
Metabotropic Glutamate ◽  
Term Potentiation ◽  
Intracellular Messenger

Glutamate signaling regulates neuronal activity and synaptic plasticity, which underlies learning and memory. In this issue of Science Signaling, Foster et al. found that metabotropic glutamate receptors mediate long-term potentiation in hippocampal neurons by mobilizing acidic endolysosomal Ca2+ stores through the intracellular messenger NAADP.

scholarly journals c-Rel, an NF- B family transcription factor, is required for hippocampal long-term synaptic plasticity and memory formation

2008 ◽  
Vol 15 (7) ◽  
pp. 539-549 ◽  
Author(s):  
H. J. Ahn ◽  
C. M. Hernandez ◽  
J. M. Levenson ◽  
F. D. Lubin ◽  
H.-C. Liou ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Synaptic Plasticity ◽  
Memory Formation

scholarly journals A screen for sleep and starvation resistance identifies a wake-promoting role for the auxiliary channel unc79

2021 ◽  
Author(s):  
Kazuma Murakami ◽  
Justin Palermo ◽  
Bethany A. Stanhope ◽  
Alex C. Keene
Keyword(s):  
Sleep Duration ◽  
Mushroom Body ◽  
Metabolic Diseases ◽  
Genetic Screen ◽  
Metabolic Function ◽  
Starvation Resistance ◽  
Pacemaker Neurons ◽  
Number Of Genes ◽  
Circadian Behavior

AbstractThe regulation of sleep and metabolism are highly interconnected, and dysregulation of sleep is linked to metabolic diseases that include obesity, diabetes, and heart disease. Further, both acute and long-term changes in diet potently impact sleep duration and quality. To identify novel factors that modulate interactions between sleep and metabolic state, we performed a genetic screen for their roles in regulating sleep duration, starvation resistance, and starvation-dependent modulation of sleep. This screen identified a number of genes with potential roles in regulating sleep, metabolism or both processes. One such gene encodes the auxiliary ion channel UNC79, which was implicated in both the regulation of sleep and starvation resistance. Genetic knockdown or mutation of unc79 results in flies with increased sleep duration, as well as increased starvation resistance. Previous findings have shown that unc79 is required in pacemaker for 24-hour circadian rhythms. Here, we find that unc79 functions in the mushroom body, but not pacemaker neurons, to regulate sleep duration and starvation resistance. Together, these findings reveal spatially localized separable functions of unc79 in the regulation of circadian behavior, sleep, and metabolic function.

scholarly journals A screen for sleep and starvation resistance identifies a wake-promoting role for the auxiliary channel unc79

2021 ◽  
Author(s):  
Kazuma Murakami ◽  
Justin Palermo ◽  
Bethany A Stanhope ◽  
Allen G Gibbs ◽  
Alex C Keene
Keyword(s):  
Sleep Duration ◽  
Mushroom Body ◽  
Metabolic Diseases ◽  
Genetic Screen ◽  
Metabolic Function ◽  
Starvation Resistance ◽  
Pacemaker Neurons ◽  
Number Of Genes ◽  
Circadian Behavior

Abstract The regulation of sleep and metabolism are highly interconnected, and dysregulation of sleep is linked to metabolic diseases that include obesity, diabetes, and heart disease. Further, both acute and long-term changes in diet potently impact sleep duration and quality. To identify novel factors that modulate interactions between sleep and metabolic state, we performed a genetic screen for their roles in regulating sleep duration, starvation resistance, and starvation-dependent modulation of sleep. This screen identified a number of genes with potential roles in regulating sleep, metabolism or both processes. One such gene encodes the auxiliary ion channel UNC79, which was implicated in both the regulation of sleep and starvation resistance. Genetic knockdown or mutation of unc79 results in flies with increased sleep duration, as well as increased starvation resistance. Previous findings have shown that unc79 is required in pacemaker for 24-hour circadian rhythms. Here, we find that unc79 functions in the mushroom body, but not pacemaker neurons, to regulate sleep duration and starvation resistance. Together, these findings reveal spatially localized separable functions of unc79 in the regulation of circadian behavior, sleep, and metabolic function.

The Effects of P75NTR on Learning Memory Mediated by Hippocampal Apoptosis and Synaptic Plasticity

2020 ◽  
Vol 26 ◽  
Author(s):  
Jun-Jie Tang ◽  
Shuang Feng ◽  
Xing-Dong Chen ◽  
Hua Huang ◽  
Min Mao ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Neurological Diseases ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Negative Effects ◽  
Apoptotic Effect ◽  
New Ideas ◽  
The Relationship

: Neurological diseases bring great mental and physical torture to the patients, and have long-term and sustained negative effects on families and society. The attention to neurological diseases is increasing, and the improvement of the material level is accompanied by an increase in the demand for mental level. The p75 neurotrophin receptor (p75NTR) is a low-affinity neurotrophin receptor and involved in diverse and pleiotropic effects in the developmental and adult central nervous system (CNS). Since neurological diseases are usually accompanied by the regression of memory, the pathogenesis of p75NTR also activates and inhibits other signaling pathways, which has a serious impact on the learning and memory of patients. The results of studies shown that p75NTR is associated with LTP/LTD-induced synaptic enhancement and inhibition, suggest that p75NTR may be involved in the progression of synaptic plasticity. And its pro-apoptotic effect is associated with activation of proBDNF and inhibition of proNGF, and TrkA/p75NTR imbalance leads to pro-survival or pro-apoptotic phenomena. It can be inferred that p75NTR mediates apoptosis in the hippocampus and amygdale, which may affect learning and memory behavior. This article mainly discusses the relationship between p75NTR and learning memory and associated mechanisms, which may provide some new ideas for the treatment of neurological diseases.

Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats

2020 ◽  
Vol 17 (4) ◽  
pp. 354-360 ◽  
Author(s):  
Yu-Xing Ge ◽  
Ying-Ying Lin ◽  
Qian-Qian Bi ◽  
Yu-Juan Chen
Keyword(s):  
Synaptic Plasticity ◽  
Temporal Lobe Epilepsy ◽  
Synaptic Vesicle ◽  
Long Term Potentiation ◽  
Synaptic Dysfunction ◽  
Over Expression ◽  
Term Potentiation ◽  
Synaptic Vesicle Protein 2A

Background: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. Objective: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. Methods: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. Results: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. Conclusion: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.

scholarly journals P044 Can an electronic prescribing system ensure clear anticoagulation discharge communication?

2019 ◽  
Vol 104 (7) ◽  
pp. e2.49-e2
Author(s):  
Susie Gage
Keyword(s):  
Patient Safety ◽  
Discharge Summary ◽  
Electronic Prescribing ◽  
List Type ◽  
Heparin Infusion ◽  
National Patient Safety Agency ◽  
High Dependency ◽  
National Patient ◽  
Discharge Summaries

AimThe National Patient Safety Agency (NPSA)1 identified heparin as a major cause of adverse events associated with adverse incidents, including some fatalities. By ensuring good communication, this should be associated with risk reduction.1 The aim of this study was to ensure there is clear anticoagulation communication on discharge, from the paediatric intensive care unit (PICU) electronic prescribing system (Philips), to the paediatric cardiac high dependency unit and paediatric cardiac ward. To investigate whether the heparin regimen complies with the hospital’s anticoagulant guidelines and if there is any deviation; that this is clearly documented. To find out if there is an indication documented for the heparin regimen chosen and if there is a clear long term plan documented for the patient, after heparin cessation.MethodsA report was generated for all patients who were prescribed a heparin infusion on PICU, between 1st January 2018 and 30th June 2018, from the Philips system. All discharge summaries from the PICU Philips system were reviewed. Only paediatric cardiac patients were included that had a heparin infusion prescribed on discharge, all other discharge summaries were excluded from the study. Each discharge summary was reviewed in the anticoagulant section; for the heparin regimen chosen, whether it complies with the hospital’s anticoagulant guidelines and if there was any deviation whether this was documented. The indication documented of which heparin regimen was chosen and whether a clear long term plan was documented after heparin cessation; for example if the patient is to be transferred onto aspirin, clopidogrel, warfarin or enoxaparin.Results82 discharge summaries were reviewed over the 6 month period between 1st January 2018 and 30th June 2018; 16 were excluded as were not paediatric cardiac, leaving 66 paediatric cardiac discharge summaries that were reviewed. 45 out of 66 (68%) complied with the hospital’s heparin anticoagulation guidelines. Of the 32% that deviated from the protocol; only 33% (7 out of 21) had a reason documented. Only 50% (33) of the summaries reviewed had an indication for anticoagulation noted on the discharge summary and 91% of discharge summaries had a long term anticoagulant plan documented.ConclusionThe electronic prescribing system can help to ensure a clear anticoagulation communication as shown by 91% of the anticoagulation long term plan being clearly documented; making it a more seamless patient transfer. On the Philips PICU electronic prescribing system there is an anticoagulant section on the discharge summary that has 3 boxes that need to be completed; heparin regimen, indication and anticoagulation long term plan. However, despite these boxes; deviations from the anticoagulant protocol were poorly documented as highlighted by only 33% having the reason highlighted in the discharge summary, only 50% of the indications were documented. Despite having prompts for this information on the discharge summary, the medical staffs needs to be aware to complete this information, in order to reduce potential medication errors and risk.ReferenceThe National Patient Safety Agency (NPSA). Actions that make anticoagulant therapy safer. NPSA; March 2007.

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