The Integrated Stress Response in Memory and Cognitive Disorders

2020 ◽  
Author(s):  
Jacqunae L. Mays ◽  
Mauro Costa-Mattioli
Keyword(s):  
Protein Synthesis ◽  
Stress Response ◽  
Cognitive Disorders ◽  
Memory Formation ◽  
Model Systems ◽  
Long Term Memory ◽  
Integrated Stress Response ◽  
Term Memory ◽  
Wide Range

The integrated stress response (ISR) is an evolutionarily conserved intracellular signaling network that responds to proteostasis defects and stress conditions by tuning protein synthesis rates. While it has been long recognized that long-term memory formation requires new protein synthesis, our understanding of the central translational control mechanisms that regulate memory formation has advanced vastly. Indeed, novel causal and convergent evidence across different species and model systems shows that the ISR serves as a universal regulator of long-term memory formation. This chapter discusses the evidence explaining how inhibition of the ISR enhances long-term memory formation while activation of the ISR prevents it. In addition, it highlights the role of the ISR in different forms of long-lasting synaptic plasticity in the brain. Finally, the chapter addresses how dysregulated ISR signaling contributes to the pathogenesis of a wide range of cognitive and neurodegenerative disorders and discusses the future prospects for therapeutically targeting the ISR for the treatment of cognitive disorders.

The integrated stress response: From mechanism to disease

Science ◽  
2020 ◽  
Vol 368 (6489) ◽  
pp. eaat5314 ◽  
Author(s):  
Mauro Costa-Mattioli ◽  
Peter Walter
Keyword(s):  
Stress Response ◽  
Metabolic Disorders ◽  
Protein Quality ◽  
Cognitive Disorders ◽  
Proper Function ◽  
Long Term Memory ◽  
Integrated Stress Response ◽  
Age Related ◽  
Wide Range

Protein quality control is essential for the proper function of cells and the organisms that they make up. The resulting loss of proteostasis, the processes by which the health of the cell’s proteins is monitored and maintained at homeostasis, is associated with a wide range of age-related human diseases. Here, we highlight how the integrated stress response (ISR), a central signaling network that responds to proteostasis defects by tuning protein synthesis rates, impedes the formation of long-term memory. In addition, we address how dysregulated ISR signaling contributes to the pathogenesis of complex diseases, including cognitive disorders, neurodegeneration, cancer, diabetes, and metabolic disorders. The development of tools through which the ISR can be modulated promises to uncover new avenues to diminish pathologies resulting from it for clinical benefit.

Differential requirement of de novo Arc protein synthesis in the insular cortex and the amygdala for safe and aversive taste long-term memory formation

2018 ◽  
Vol 342 ◽  
pp. 89-93 ◽  
Author(s):  
Kioko Guzmán-Ramos ◽  
Archana Venkataraman ◽  
Jean-Pascal Morin ◽  
Daniel Osorio-Gómez ◽  
Federico Bermúdez-Rattoni
Keyword(s):  
Protein Synthesis ◽  
De Novo ◽  
Insular Cortex ◽  
Memory Formation ◽  
Long Term Memory ◽  
Term Memory ◽  
Aversive Taste

scholarly journals New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Roi Levy ◽  
David Levitan ◽  
Abraham J Susswein
Keyword(s):  
Protein Synthesis ◽  
Memory Formation ◽  
Long Term Memory ◽  
Learning Paradigm ◽  
Translation Memory ◽  
Sleep Phase ◽  
Term Memory ◽  
New Learning ◽  
Effective Training

Brief experiences while a memory is consolidated may capture the consolidation, perhaps producing a maladaptive memory, or may interrupt the consolidation. Since consolidation occurs during sleep, even fleeting experiences when animals are awakened may produce maladaptive long-term memory, or may interrupt consolidation. In a learning paradigm affecting Aplysia feeding, when animals were trained after being awakened from sleep, interactions between new experiences and consolidation were prevented by blocking long-term memory arising from the new experiences. Inhibiting protein synthesis eliminated the block and allowed even a brief, generally ineffective training to produce long-term memory. Memory formation depended on consolidative proteins already expressed before training. After effective training, long term memory required subsequent transcription and translation. Memory formation during the sleep phase was correlated with increased CREB1 transcription, but not CREB2 transcription. Increased C/EBP transcription was a correlate of both effective and ineffective training and of treatments not producing memory.

Drug inhibition of memory formation in chickens I. Long-term memory

1971 ◽  
Vol 178 (1053) ◽  
pp. 439-454 ◽  
Keyword(s):  
Protein Synthesis ◽  
Learning Task ◽  
Memory Formation ◽  
Long Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Permanent Storage ◽  
Drug Inhibition ◽  
Two Stages

1. A one-trial passive avoidance learning task using day-old chickens is described and shown to be suitable for testing the effects of direct intracranial injection of drugs. 2. Inhibitors of the sodium pump have been found to block the formation of long-term memory only if present at the time of learning. 3. Inhibitors of protein synthesis will prevent long-term memory formation even if they are administered after learning. 4. From this, there appear to be at least two stages in the formation of memory. A short-term phase dependent on membrane mechanisms leads to permanent storage dependent on protein synthesis.

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