ArticleScience translational medicine2012
Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism.
Article in Science translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
152 citing papers in PubMed, 253 citations in OpenAlex.
- STX209 (arbaclofen) for autism spectrum disorders: an 8-week open-label study.Journal of autism and developmental disorders · 2014Trial
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- Choroid plexus apocrine secretion shapes CSF proteome during mouse brain development.Nature neuroscience · 2025Article
- Acute administration of lovastatin had no pronounced effect on motor abilities, motor coordination, gait nor simple cognition in a mouse model of Angelman syndrome.Journal of neurodevelopmental disorders · 2025Article
- Discovery of Thieno[3,2-ACS medicinal chemistry letters · 2025Article
- Peptidomimetic inhibitors targeting TrkB/PSD-95 signaling improves cognition and seizure outcomes in an Angelman Syndrome mouse model.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Non-ionotropic signaling through the NMDA receptor GluN2B carboxy-terminal domain drives dendritic spine plasticity and reverses fragile X phenotypes.Cell reports · 2025Article
- Molecular Pathways, Neural Circuits and Emerging Therapies for Self-Injurious Behaviour.International journal of molecular sciences · 2025Review
- Discovery of 4-(5-Membered)Heteroarylether-6-methylpicolinamide Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5.ACS medicinal chemistry letters · 2024Article
- Neural substrates for regulating self-grooming behavior in rodents.Journal of Zhejiang University. Science. B · 2024Review
- Developmental exposure to the Fox River PCB mixture modulates behavior in juvenile mice.Neurotoxicology · 2024Article
- Female-specific dysfunction of sensory neocortical circuits in a mouse model of autism mediated by mGluR5 and estrogen receptor α.Cell reports · 2024Article
- Gene editing in small and large animals for translational medicine: a review.Animal reproduction · 2024Review
- The role of neurotrophic factors in novel, rapid psychiatric treatments.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Group I and group II metabotropic glutamate receptors are upregulated in the synapses of infant rats prenatally exposed to valproic acid.Psychopharmacology · 2023Article
- Hyperthermia elevates brain temperature and improves behavioural signs in animal models of autism spectrum disorder.Molecular autism · 2023Article
- Modernising autism spectrum disorder model engineering and treatmentWorld journal of clinical cases · 2023Review
- Review
92 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Neurodevelopmental disorders such as autism and fragile X syndrome were long thought to be medically untreatable, on the assumption that brain dysfunctions were immutably hardwired before diagnosis. Recent revelations that many cases of autism are caused by mutations in genes that control the ongoing formation and maturation of synapses have challenged this dogma. Antagonists of metabotropic glutamate receptor subtype 5 (mGluR5), which modulate excitatory neurotransmission, are in clinical trials for fragile X syndrome, a major genetic cause of intellectual disabilities. About 30% of patients with fragile X syndrome meet the diagnostic criteria for autism. Reasoning by analogy, we considered the mGluR5 receptor as a potential target for intervention in autism. We used BTBR T+tf/J (BTBR) mice, an established model with robust behavioral phenotypes relevant to the three diagnostic behavioral symptoms of autism--unusual social interactions, impaired communication, and repetitive behaviors--to probe the efficacy of a selective negative allosteric modulator of the mGluR5 receptor, GRN-529. GRN-529 reduced repetitive behaviors in three cohorts of BTBR mice at doses that did not induce sedation in control assays of open field locomotion. In addition, the same nonsedating doses reduced the spontaneous stereotyped jumping that characterizes a second inbred strain of mice, C58/J. Further, GRN-529 partially reversed the striking lack of sociability in BTBR mice on some parameters of social approach and reciprocal social interactions. These findings raise the possibility that a single targeted pharmacological intervention may alleviate multiple diagnostic behavioral symptoms of autism.
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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.