ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2026
Lithium as a therapeutic strategy for SNAP25 encephalopathies via modulation of homeostatic plasticity.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Synaptic vesicle fusion is orchestrated by the soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) complex. The SNARE complex includes SNAP25, synaptobrevin-2, and syntaxin-1. This machinery drives action potential-evoked release, as well as the majority of spontaneous release. Mutations in components of the SNARE machinery can differentially affect spontaneous or evoked release and result in severe neurodevelopmental phenotypes, as exemplified by SNAP25 encephalopathies that arise from mutations in the SNAP25 gene. Among various pathogenic SNAP25 variants, L50S, V48F, and D166Y increase spontaneous glutamate release that destabilizes network activity. Patients who carry these variants develop recurrent seizures that are refractory to conventional antiepileptic drugs, which primarily act on components of evoked neurotransmission and leave spontaneous release abnormalities unaddressed. To surmount this limitation, we explored a strategy targeting homeostatic plasticity mechanisms with lithium, which has been shown to downscale postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR). In vitro, lithium corrected cellular phenotypes in neurons expressing SNAP25 variants. In vivo, we generated a knock-in mouse model recapitulating the SNAP25 L50S mutation to test these results. These mice displayed increased neonatal mortality, infertility, hypomobility, frequent seizure activity, anxiety-like behavior, social deficits, and impaired learning and memory. Chronic lithium treatment reduced seizure frequency and ameliorated long-term memory and locomotor activity. Taken together, lithium alleviated synaptic and behavioral disturbances driven by pathological spontaneous glutamate release by inducing homeostatic AMPAR downscaling. Thus, this work provides a mechanistically grounded therapeutic strategy for SNAP25 encephalopathies and other disorders characterized by elevated spontaneous glutamate release.
Identifiers
42661025What OpenQuestion holds
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.