The type 2 ryanodine receptor/calcium release channel (RyR2), required for excitation-contraction coupling in the heart, is abundant in the brain. Chronic stress induces catecholamine biosynthesis and release, stimulating β-adrenergic receptors and activating cAMP signaling pathways in neurons. In a murine chronic restraint stress model, neuronal RyR2 were phosphorylated by protein kinase A (PKA), oxidized, and nitrosylated, resulting in depletion of the stabilizing subunit calstabin2 (FKBP12.6) from the channel complex and intracellular calcium leak. Stress-induced cognitive dysfunction, including deficits in learning and memory, and reduced long-term potentiation (LTP) at the hippocampal CA3-CA1 connection were rescued by oral administration of S107, a compound developed in our laboratory that stabilizes RyR2-calstabin2 interaction, or by genetic ablation of the RyR2 PKA phosphorylation site at serine 2808. Thus, neuronal RyR2 remodeling contributes to stress-induced cognitive dysfunction. Leaky RyR2 could be a therapeutic target for treatment of stress-induced cognitive dysfunction.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690518 | PMC |
| http://dx.doi.org/10.1016/j.cell.2012.06.052 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Characterizing Oxidative Stress induced by Aβ Oligomers and the Protective Role of Carnosine in Primary Mixed Glia Cultures.
Free Radic Biol Med
January 2025
Department of Drug and Health Sciences, University of Catania, Catania, Italy; Unit of Neuropharmacology and Translational Neurosciences, Oasi Research Institute-IRCCS, Troina, Italy. Electronic address:
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss. A critical aspect of AD pathology is represented by oxidative stress, which significantly contributes to neuronal damage and death. Microglia and astrocytes, the primary glial cells in the brain, are crucial for managing oxidative stress and supporting neuronal function.
View Article and Find Full Text PDFThe impact of induced stress on reactive and proactive control in depression.
PeerJ
January 2025
Department of Psychology, Aichi University of Education, Kariya, Aichi, Japan.
Background: Depression, a widespread mental health issue, is often marked by impaired cognitive control, particularly in managing proactive and reactive processes. The Dual Mechanisms of Control (DMC) framework differentiates between these two modes of cognitive control: proactive control involves sustained goal maintenance, while reactive control is more stimulus-driven and transient. Stress, known to exacerbate cognitive dysfunction in depression, may influence the balance between these control processes, though the specific effects remain poorly understood.
View Article and Find Full Text PDFCHOP-Mediated Disruption of Hippocampal Synaptic Plasticity and Neuronal Activity Contributes to Chronic Pain-Related Cognitive Deficits.
CNS Neurosci Ther
January 2025
Department of Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Objectives: Endoplasmic reticulum (ER) stress-induced protein homeostasis perturbation is a core pathological element in the pathogenesis of neurodegenerative diseases. This study aims to clarify the unique role played by C/EBP homologous protein (CHOP) as a biomarker of the unfolded protein response (UPR) in the etiology of chronic pain and related cognitive impairments following chronic constrictive nerve injury (CCI).
Methods: The memory capability following CCI was assessed utilizing the Morris water maze (MWM) and fear conditioning test (FCT).
Prenatal stress alters mouse offspring dorsal striatal development and placental function in sex-specific ways.
J Psychiatr Res
January 2025
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA; Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, 52246, USA; Yale Child Study Center, Yale School of Medicine, New Haven, CT, 06510, USA. Electronic address:
Prenatal stress is a risk factor for neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD). However, how early stress modification of brain development contributes to this pathophysiology is poorly understood. Ventral forebrain regions such as dorsal striatum are of particular interest: dorsal striatum modulates movement and cognition, is altered in NDDs, and has a primarily GABAergic population.
View Article and Find Full Text PDFLeft ventromedial prefrontal cortex inhibitory rTMS as an anti-stress intervention in opioid use disorder: Trial design.
Contemp Clin Trials Commun
February 2025
Dept. of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI, USA.
Background: In people with substance use disorders (SUDs), stress-exposure can impair executive function, and increase craving and likelihood of drug-use recurrence. Research shows that acute stressors increase drug-seeking behavior; however, mechanisms underlying this effect are incompletely understood. The Competing Neurobehavioral Decisions System theory posits that persons with SUDs may have hyperactive limbic reward circuitry and hypoactive executive control circuitry.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!