ArticleBrain : a journal of neurology2024
Scn1a haploinsufficiency in the prefrontal cortex leads to cognitive impairment and depressive phenotype.
Article in Brain : a journal of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Lidocaine for Depressive Symptoms and Comorbid Pain: A Narrative Review of Mechanisms, Evidence, and Safety.Drug design, development and therapy · 2026Review
- Depression mediated sleep disturbances and cognitive decline in Parkinson's disease patient.Frontiers in neuroscience · 2026Article
- Natural History of Children and Adolescents With Dravet Syndrome: A 24-Month Follow-Up.Neurology · 2025Observational
- Transcriptomic analyses of human brains with Alzheimer's disease identified dysregulated epilepsy-causing genes.Epilepsy & behavior : E&B · 2025Article
- Brain connectivity and transcriptional changes induced by rTMS in first-episode major depressive disorder.Translational psychiatry · 2025Article
- Astrocytic pleiotrophin deficiency in the prefrontal cortex contributes to stress-induced depressive-like responses in male mice.Nature communications · 2025Article
- Altered synaptic homeostasis: a key factor in the pathophysiology of depression.Cell & bioscience · 2025Review
- Transcriptomic analyses of human brains with Alzheimer's disease identified dysregulated epilepsy-causing genes.medRxiv : the preprint server for health sciences · 2025Article
- EZH2-mediated H3K27me3 links microbial inosine loss to depression: a gut-brain epigenetic switch.Theranostics · 2025Article
- The cumulative impact of seizures: the science underlying how seizures beget seizures.Frontiers in neurologyReview
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Authors and funding
12 authors.
Funding
Abstract
Altered development and function of the prefrontal cortex (PFC) during adolescence is implicated in the origin of mental disorders. Deficits in the GABAergic system prominently contribute to these alterations. Nav1.1 is a voltage-gated Na+ channel critical for normal GABAergic activity. Here, we studied the role of Nav1.1 in PFC function and its potential relationship with the aetiology of mental disorders. Dysfunction of Nav1.1 activity in the medial PFC (mPFC) of adolescent mice enhanced the local excitation/inhibition ratio, resulting in epileptic activity, cognitive deficits and depressive-like behaviour in adulthood, along with a gene expression profile linked to major depressive disorder (MDD). Additionally, it reduced extracellular serotonin concentration in the dorsal raphe nucleus and brain-derived neurotrophic factor expression in the hippocampus, two MDD-related brain areas beyond the PFC. We also observed alterations in oscillatory activity and impaired hippocampal-mPFC coherence during sleep. Finally, we found reduced expression levels of SCN1A, the gene encoding Nav1.1, in post-mortem PFC samples from human MDD subjects. Collectively, our results provide a novel mechanistic framework linking adolescence-specific alterations in Nav1.1 function in the PFC to the pathogenesis of epilepsy and comorbidities such as cognitive impairment and depressive disorders.
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