ArticleJCI insight2019
Neuronal network dysfunction precedes storage and neurodegeneration in a lysosomal storage disorder.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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
14 citing papers in PubMed, 28 citations in OpenAlex.
- Translatable electrophysiological and behavioral abnormalities in a humanized model of SYNGAP1-disorder.Molecular psychiatry · 2026Article
- Functional ultrasound imaging reveals early pathway-specific reorganization of central visual circuits in a mouse model of Batten disease.Neurobiology of disease · 2026Article
- Distinct Auditory Thalamocortical Pathologies Underlie Emerging Neurophysiological Dysfunction in a Cln3 Mouse Model of Batten Disease.bioRxiv : the preprint server for biology · 2026Article
- Reversible synaptic deficits in early-stage batten disease.Journal of translational medicine · 2026Article
- CLN3 disease disrupts very early postnatal hippocampal maturation.Scientific reports · 2025Article
- GABATranslational psychiatry · 2024Article
- Early postnatal administration of an AAV9 gene therapy is safe and efficacious in CLN3 disease.Frontiers in genetics · 2023Article
- Tubulin deacetylase NDST3 modulates lysosomal acidification: Implications in neurological diseases.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- Neuronal genetic rescue normalizes brain network dynamics in a lysosomal storage disorder despite persistent storage accumulation.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Transmembrane Batten Disease Proteins Interact With a Shared Network of Vesicle Sorting Proteins, Impacting Their Synaptic Enrichment.Frontiers in neuroscience · 2022Article
- CLN3, at the crossroads of endocytic trafficking.Neuroscience letters · 2021Article
- Ischemia-induced upregulation of autophagy preludes dysfunctional lysosomal storage and associated synaptic impairments in neurons.Autophagy · 2021Article
- Aged heterozygous Cdkl5 mutant mice exhibit spontaneous epileptic spasms.Experimental neurology · 2020Article
- Neuropathophysiology of Lysosomal Storage Diseases: Synaptic Dysfunction as a Starting Point for Disease Progression.Journal of clinical medicine · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Accumulation of lysosomal storage material and late-stage neurodegeneration are hallmarks of lysosomal storage disorders (LSDs) affecting the brain. Yet, for most LSDs, including CLN3 disease, the most common form of childhood dementia, it is unclear what mechanisms drive neurologic symptoms. Do deficits arise from loss of function of the mutated protein or toxicity from storage accumulation? Here, using in vitro voltage-sensitive dye imaging and in vivo electrophysiology, we find progressive hippocampal dysfunction occurs before notable lysosomal storage and neuronal loss in 2 CLN3 disease mouse models. Pharmacologic reversal of lysosomal storage deposition in young mice does not rescue this circuit dysfunction. Additionally, we find that CLN3 disease mice lose an electrophysiologic marker of new memory encoding - hippocampal sharp-wave ripples. This discovery, which is also seen in Alzheimer's disease, suggests the possibility of a shared electrophysiologic signature of dementia. Overall, our data describe new insights into previously unknown network-level changes occurring in LSDs affecting the central nervous system and highlight the need for new therapeutic interventions targeting early circuit defects.
Indexed as
Identifiers
What 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.