ArticleFrontiers in molecular neuroscience2021
Risperidone Mitigates Enhanced Excitatory Neuronal Function and Repetitive Behavior Caused by an ASD-Associated Mutation of SIK1.
Article in Frontiers in molecular neuroscience, 2021. 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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18 citing papers in PubMed, 20 citations in OpenAlex.
- Long-term effects of adolescent risperidone treatment on the mouse cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- SIK2 mediated mitochondrial homeostasis in spinal cord injury: modulating oxidative stress and the AIM2 inflammasome via CRTC1/CREB signaling.Journal of neuroinflammation · 2025Article
- Article
- Developmental deficits, synapse and dendritic abnormalities in a Clcn4 KO autism mice model: endophenotypic target for ASD.Translational psychiatry · 2025Article
- 3KO-NSCs ameliorate behavioral deficits and modulate gut microbiota in a VPA-induced C57BL/6 mouse model of autism.Frontiers in immunology · 2025Article
- Deep-Learning-Based Analysis Reveals a Social Behavior Deficit in Mice Exposed Prenatally to Nicotine.Cells · 2024Article
- Unveiling the Role of Sik1 in Osteoblast Differentiation: Implications for Osteoarthritis.Molecular and cellular biology · 2024Article
- Adult neurogenesis in the ventral hippocampus decreased among animal models of neurodevelopmental disorders.Frontiers in neural circuits · 2024Article
- Protective effects of the saltZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Blocking salt-inducible kinases with YKL-06-061 prevents PTZ-induced seizures in mice.Brain and behavior · 2023Article
- Deficiency of salt-inducible kinase 2 (SIK2) promotes immune injury by inhibiting the maturation of lymphocytes.MedComm · 2023Article
- Diverse Clinical Phenotypes ofGenes · 2023Review
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
- A parathyroid hormone/salt-inducible kinase signaling axis controls renal vitamin D activation and organismal calcium homeostasis.The Journal of clinical investigation · 2023Article
- An Epilepsy-Associated Mutation of Salt-Inducible Kinase 1 Increases the Susceptibility to Epileptic Seizures and Interferes with Adrenocorticotropic Hormone Therapy for Infantile Spasms in Mice.International journal of molecular sciences · 2022Article
- Novel mutation of SIK1 gene causing a mild form of pediatric epilepsy in a Chinese patient.Metabolic brain disease · 2022Article
- Repetitive Restricted Behaviors in Autism Spectrum Disorder: From Mechanism to Development of Therapeutics.Frontiers in neuroscience · 2022Review
- Article
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9 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Six mutations in the salt-inducible kinase 1 (SIK1)-coding gene have been identified in patients with early infantile epileptic encephalopathy (EIEE-30) accompanied by autistic symptoms. Two of the mutations are non-sense mutations that truncate the C-terminal region of SIK1. It has been shown that the C-terminal-truncated form of SIK1 protein affects the subcellular distribution of SIK1 protein, tempting to speculate the relevance to the pathophysiology of the disorders. We generated SIK1-mutant (SIK1-MT) mice recapitulating the C-terminal-truncated mutations using CRISPR/Cas9-mediated genome editing. SIK1-MT protein was distributed in the nucleus and cytoplasm, whereas the distribution of wild-type SIK1 was restricted to the nucleus. We found the disruption of excitatory and inhibitory (E/I) synaptic balance due to an increase in excitatory synaptic transmission and enhancement of neural excitability in the pyramidal neurons in layer 5 of the medial prefrontal cortex in SIK1-MT mice. We also found the increased repetitive behavior and social behavioral deficits in SIK1-MT mice. The risperidone administration attenuated the neural excitability and excitatory synaptic transmission, but the disrupted E/I synaptic balance was unchanged, because it also reduced the inhibitory synaptic transmission. Risperidone also eliminated the repetitive behavior but not social behavioral deficits. These results indicate that risperidone has a role in decreasing neuronal excitability and excitatory synapses, ameliorating repetitive behavior in the SIK1-truncated mice.
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