ArticleMolecular psychiatry2004
Stress-induced alternative splicing of acetylcholinesterase results in enhanced fear memory and long-term potentiation.
Article in Molecular psychiatry, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 128 citations in OpenAlex.
- Unlocking the Potential of Isatin Scaffolds in Acetylcholinesterase Inhibition.Archiv der Pharmazie · 2026Review
- Translational assessment of butyrylcholinesterase activity as a diagnostic biomarker for depression using a chemiluminescent probe.Scientific reports · 2026Article
- Re-assessing host manipulation in Toxoplasma: the underexplored role of sexual transmission - evidence, mechanisms, implications.Folia parasitologica · 2025Review
- In silico analysis of the use of solanine derivatives as a treatment for Alzheimer's disease.Heliyon · 2024Article
- The roles of RACK1 in the pathogenesis of Alzheimer's disease.Journal of biomedical research · 2024Article
- Physical exercise and mitochondrial function: New therapeutic interventions for psychiatric and neurodegenerative disorders.Frontiers in neurology · 2022Review
- Cholinergic neurotransmission in the basolateral amygdala during cued fear extinction.Neurobiology of stress · 2020Article
- Cholinergic Stress Signals Accompany MicroRNA-Associated Stereotypic Behavior and Glutamatergic Neuromodulation in the Prefrontal Cortex.Biomolecules · 2020Article
- Stress-mediated convergence of splicing landscapes in male and female rock doves.BMC genomics · 2020Article
- Acute restraint stress reverses impaired LTP in the hippocampal CA1 region in mouse models of Alzheimer's disease.Scientific reports · 2019Article
- Differential expression of acetylcholinesterase 1 in response to various stress factors in honey bee workers.Scientific reports · 2019Article
- Increased Active OMI/HTRA2 Serine Protease Displays a Positive Correlation with Cholinergic Alterations in the Alzheimer's Disease Brain.Molecular neurobiology · 2019Article
- Cholinergic regulation of mood: from basic and clinical studies to emerging therapeutics.Molecular psychiatry · 2019Review
- Identification of new allosteric sites and modulators of AChE through computational and experimental tools.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- Acute and long-term consequences of exposure to organophosphate nerve agents in humans.Epilepsia · 2018Review
- Evaluate neuroprotective effect of silibinin using chronic unpredictable stress (cus) model.International journal of physiology, pathophysiology and pharmacology · 2018Article
- Impairments in laterodorsal tegmentum to VTA projections underlie glucocorticoid-triggered reward deficits.eLife · 2017Article
- ACBD2/ECI2-Mediated Peroxisome-Mitochondria Interactions in Leydig Cell Steroid Biosynthesis.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Strain dependent effects of conditioned fear in adult C57Bl/6 and Balb/C mice following postnatal exposure to chlorpyrifos: relation to expression of brain acetylcholinesterase mRNA.Frontiers in behavioral neuroscience · 2015Article
- Neuromodulation by acetylcholine: examples from schizophrenia and depression.Current opinion in neurobiology · 2014Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stress insults intensify fear memory; however, the mechanism(s) facilitating this physiological response is still unclear. Here, we report the molecular, neurophysiological and behavioral findings attributing much of this effect to alternative splicing of the acetylcholinesterase (AChE) gene in hippocampal neurons. As a case study, we explored immobilization-stressed mice with intensified fear memory and enhanced long-term potentiation (LTP), in which alternative splicing was found to induce overproduction of neuronal 'readthrough' AChE-R (AChE-R). Selective downregulation of AChE-R mRNA and protein by antisense oligonucleotides abolished the stress-associated increase in AChE-R, the elevation of contextual fear and LTP in the hippocampal CA1 region. Reciprocally, we intrahippocampally injected a synthetic peptide representing the C-terminal sequence unique to AChE-R. The injected peptide, which has been earlier found to exhibit no enzymatic activity, was incorporated into cortical, hippocampal and basal nuclei neurons by endocytosis and retrograde transport and enhanced contextual fear. Compatible with this hypothesis, inherited AChE-R overexpression in transgenic mice resulted in perikaryal clusters enriched with PKCbetaII, accompanied by PKC-augmented LTP enhancement. Our findings demonstrate a primary role for stress-induced alternative splicing of the AChE gene to elevated contextual fear and synaptic plasticity, and attribute to the AChE-R splice variant a major role in this process.
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