ArticleMolecular psychiatry2023
Autistic-like behavior and cerebellar dysfunction in Bmal1 mutant mice ameliorated by mTORC1 inhibition.
Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 55 citations in OpenAlex.
- Large-Scale Neuroimaging and Genetic Analyses of the Human Thalamus in Loneliness.Biological psychiatry global open science · 2026Article
- Chronic sleep deprivation promotes drug-resistant epilepsy via the BMAL1-mTOR-P-gp axis.Epilepsia open · 2026Article
- Circadian Phase Modulates Embryonic Susceptibility to Bisphenol A-Induced ASD-Related Behavioral Alterations viaToxics · 2026Article
- Reciprocal regulation between autism risk gene POGZ and circadian clock.JCI insight · 2026Article
- Bcl11a deficiency in cerebellar Purkinje cells causes ataxia and autistic-like behavior by altering Vav3.Molecular psychiatry · 2026Article
- Circadian Clock Dysfunction Exacerbate Autistic-Like Behaviour and Wnt/β-Catenin Signalling Dysregulation in ASD Mice and Treatment of Melatonin.Journal of cellular and molecular medicine · 2026Article
- Repetitive unidirectional spinal tactile stimulation engages microglial Bmal1 pathways to promote synaptic remodeling in the mPFC of adolescent VPA-exposed mice.Journal of neuroinflammation · 2025Article
- Core Circadian Protein BMAL1: Implication for Nervous System Functioning and Its Diseases.Brain sciences · 2025Review
- Circadian rhythms are disrupted in patients and preclinical models of Machado-Joseph disease.Brain : a journal of neurology · 2025Article
- Autism Spectrum Disorder: The Cerebellum, Genes, and Pathways.Neurology international · 2025Review
- A Protocol to Assess Time-of-Day-Dependent Learning and Memory in Mice Using the Novel Object Recognition Test.Bio-protocol · 2025Article
- Effect of gestational exposure to dim light at night on the behavior of rat dams and offspring.Scientific reports · 2025Article
- The Prevalence and Clinical Significance of Toe Walking in Autism Spectrum Disorder: A Cross-Sectional Study in an Italian Pediatric Sample.Medicina (Kaunas, Lithuania) · 2025Observational
- Knockout of Bmal1 in dopaminergic neurons induces ADHD-like symptoms via hyperactive dopamine signaling in male mice.Behavioral and brain functions : BBF · 2025Article
- Bmal1 Modulates Striatal cAMP Signaling and Motor Learning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Increased Temporal Variability of Gait in ASD: A Motion Capture and Machine Learning Analysis.Biology · 2025Article
- Mdga2 deficiency leads to an aberrant activation of BDNF/TrkB signaling that underlies autism-relevant synaptic and behavioral changes in mice.PLoS biology · 2025Article
- Decoding Multifaceted Roles of Sleep-Related Genes as Molecular Bridges in Chronic Disease Pathogenesis.International journal of molecular sciences · 2025Review
- Gene expression differences in the olfactory bulb associated with differential social interactions and olfactory deficits in Pax6 heterozygous mice.Biology open · 2025Article
- The transcription factor TCF4 regulates the miR-494-3p/THBS1 axis in the fibrosis of pathologic scars.Archives of dermatological research · 2025Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
Although circadian and sleep disorders are frequently associated with autism spectrum disorders (ASD), it remains elusive whether clock gene disruption can lead to autistic-like phenotypes in animals. The essential clock gene Bmal1 has been associated with human sociability and its missense mutations are identified in ASD. Here we report that global Bmal1 deletion led to significant social impairments, excessive stereotyped and repetitive behaviors, as well as motor learning disabilities in mice, all of which resemble core behavioral deficits in ASD. Furthermore, aberrant cell density and immature morphology of dendritic spines were identified in the cerebellar Purkinje cells (PCs) of Bmal1 knockout (KO) mice. Electrophysiological recordings uncovered enhanced excitatory and inhibitory synaptic transmission and reduced firing rates in the PCs of Bmal1 KO mice. Differential expression of ASD- and ataxia-associated genes (Ntng2, Mfrp, Nr4a2, Thbs1, Atxn1, and Atxn3) and dysregulated pathways of translational control, including hyperactivated mammalian target of rapamycin complex 1 (mTORC1) signaling, were identified in the cerebellum of Bmal1 KO mice. Interestingly, the antidiabetic drug metformin reversed mTORC1 hyperactivation and alleviated major behavioral and PC deficits in Bmal1 KO mice. Importantly, conditional Bmal1 deletion only in cerebellar PCs was sufficient to recapitulate autistic-like behavioral and cellular changes akin to those identified in Bmal1 KO mice. Together, these results unveil a previously unidentified role for Bmal1 disruption in cerebellar dysfunction and autistic-like behaviors. Our findings provide experimental evidence supporting a putative role for dysregulation of circadian clock gene expression in the pathogenesis of ASD.
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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.