ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Impaired hippocampal neuroligin-2 function by chronic stress or synthetic peptide treatment is linked to social deficits and increased aggression.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Contributing Factors and Induced Outcomes of Psychological Stress Response in Stroke Survivors: A Systematic Review.Frontiers in neurology · 2022Pooled it
- Modeling NDD-Associated NLGN2 Depletion Using CRISPR/Cas13 Reveals Exaggerated Process Elongation Mediated by the CCDC88A-G Protein-ELMO Axis.International journal of molecular sciences · 2026Article
- Attack Repertoires in Outbred Male CD1-Mice Are Associated with Nucleus Accumbens Neuroligin-2.eNeuro · 2026Article
- Neuroligin-2-Dependent Adhesion Defines a Molecular Checkpoint for Inhibitory Synaptic Plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Insights into Dysregulated GABAergic Synapses and Depression: A Complex and Evolving Relationship.Advances in experimental medicine and biology · 2026Review
- Genetic variation influences food-sharing sociability in honey bees.PLoS biology · 2025Article
- Neural Excitatory/Inhibitory Imbalance in Motor Aging: From Genetic Mechanisms to Therapeutic Challenges.Biology · 2025Review
- I "Gut" Rhythm: the microbiota as a modulator of the stress response and circadian rhythms.The FEBS journal · 2025Review
- A Peptide Motif Covering Splice Site B in Neuroligin-1 Binds to Aβ and Acts as a Neprilysin Inhibitor.Molecular neurobiology · 2025Article
- Reversing anxiety by targeting a stress-responsive signaling pathway.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Induced Inflammatory and Oxidative Markers in Cerebral Microvasculature by Mentally Depressive Stress.Mediators of inflammation · 2023Article
- Neuroligins in neurodevelopmental conditions: how mouse models ofNeuronal signaling · 2022Article
- Prenatal glucocorticoid exposure selectively impairs neuroligin 1-dependent neurogenesis by suppressing astrocytic FGF2-neuronal FGFR1 axis.Cellular and molecular life sciences : CMLS · 2022Article
- Age-Dependent Effects of Chronic Stress on Zebrafish Behavior and Regeneration.Frontiers in physiology · 2022Article
- Celastrol Attenuates Learning and Memory Deficits in an Alzheimer's Disease Rat Model.BioMed research international · 2021Article
- Dietary phytochemicals modulate experience-dependent changes in Neurexin gene expression and alternative splicing in mice after chronic variable stress exposure.European journal of pharmacology · 2020Article
- Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies.Neuropharmacology · 2020Review
- Revisiting the Stress Concept: Implications for Affective Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Review
- Understanding intellectual disability and autism spectrum disorders from common mouse models: synapses to behaviour.Open biology · 2019Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroligins (NLGNs) are cell adhesion molecules that are important for proper synaptic formation and functioning, and are critical regulators of the balance between neural excitation/inhibition (E/I). Mutations in NLGNs have been linked to psychiatric disorders in humans involving social dysfunction and are related to similar abnormalities in animal models. Chronic stress increases the likelihood for affective disorders and has been shown to induce changes in neural structure and function in different brain regions, with the hippocampus being highly vulnerable to stress. Previous studies have shown evidence of chronic stress-induced changes in the neural E/I balance in the hippocampus. Therefore, we hypothesized that chronic restraint stress would lead to reduced hippocampal NLGN-2 levels, in association with alterations in social behavior. We found that rats submitted to chronic restraint stress in adulthood display reduced sociability and increased aggression. This occurs along with a reduction of NLGN-2, but not NLGN-1 expression (as shown with western blot, immunohistochemistry, and electron microscopy analyses), throughout the hippocampus and detectable in different layers of the CA1, CA3, and DG subfields. Furthermore, using synthetic peptides that comprise sequences in either NLGN-1 (neurolide-1) or NLGN-2 (neurolide-2) involved in the interaction with their presynaptic partner neurexin (NRXN)-1, intra-hippocampal administration of neurolide-2 led also to reduced sociability and increased aggression. These results highlight hippocampal NLGN-2 as a key molecular substrate regulating social behaviors and underscore NLGNs as promising targets for the development of novel drugs for the treatment of dysfunctional social behaviors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.