ArticleNeurobiology of disease2015
Seizure-dependent mTOR activation in 5-HT neurons promotes autism-like behaviors in mice.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 24 citations in OpenAlex.
- Intersection of COVID-19 and Alzheimer's Disease: Genetic Insights and Neuropathological Consequences.Biochemical genetics · 2026Review
- Changes in ApoE and TIMP-1 expression correlate with outer blood-retinal barrier disruption in an in vitro model of retinal aging.GeroScience · 2026Article
- Mdga2 deficiency leads to an aberrant activation of BDNF/TrkB signaling that underlies autism-relevant synaptic and behavioral changes in mice.PLoS biology · 2025Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Is tuberous sclerosis complex-associated autism a preventable and treatable disorder?World journal of pediatrics : WJP · 2024Review
- Sudden Unexpected Death in Epilepsy and Respiratory Defects in a Mouse Model of DEPDC5-Related Epilepsy.Annals of neurology · 2023Article
- Epileptogenesis in tuberous sclerosis complex-related developmental and epileptic encephalopathy.Brain : a journal of neurology · 2023Review
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- The diverse role of the raphe 5-HTergic systems in epilepsy.Acta pharmacologica Sinica · 2022Review
- Current Approaches and Future Directions for the Treatment of mTORopathies.Developmental neuroscience · 2021Review
- Effects of antiepileptic drugs in a new TSC/mTOR-dependent epilepsy mouse model.Annals of clinical and translational neurology · 2019Article
- Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model.Scientific reports · 2018Article
- Autism, epilepsy, and synaptopathies: a not rare association.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2017Review
- Cellular and Circuitry Bases of Autism: Lessons Learned from the Temporospatial Manipulation of Autism Genes in the Brain.Neuroscience bulletin · 2017Review
- PI3K-mTOR-S6K Signaling Mediates Neuronal Viability via Collapsin Response Mediator Protein-2 Expression.Frontiers in molecular neuroscience · 2017Article
- Monogenic mouse models of autism spectrum disorders: Common mechanisms and missing links.Neuroscience · 2016Review
- A novel mouse model of tuberous sclerosis complex (TSC): eye-specific Tsc1-ablation disrupts visual-pathway development.Disease models & mechanisms · 2015Article
- Tuberous Sclerosis: A New Frontier in Targeted Treatment of Autism.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2015Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Epilepsy and autism spectrum disorder (ASD) are common comorbidities of one another. Despite the prevalent correlation between the two disorders, few studies have been able to elucidate a mechanistic link. We demonstrate that forebrain specific Tsc1 deletion in mice causes epilepsy and autism-like behaviors, concomitant with disruption of 5-HT neurotransmission. We find that epileptiform activity propagates to the raphe nuclei, resulting in seizure-dependent hyperactivation of mTOR in 5-HT neurons. To dissect whether mTOR hyperactivity in 5-HT neurons alone was sufficient to recapitulate an autism-like phenotype we utilized Tsc1flox/flox;Slc6a4-cre mice, in which mTOR is restrictively hyperactivated in 5-HT neurons. Tsc1flox/flox;Slc6a4-cre mice displayed alterations of the 5-HT system and autism-like behaviors, without causing epilepsy. Rapamycin treatment in these mice was sufficient to rescue the phenotype. We conclude that the spread of seizure activity to the brainstem is capable of promoting hyperactivation of mTOR in the raphe nuclei, which in turn promotes autism-like behaviors. Thus our study provides a novel mechanism describing how epilepsy can contribute to the development of autism-like behaviors, suggesting new therapeutic strategies for 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.