PUBLICATION

Trehalose Ameliorates Zebrafish Emotional and Social Deficits Caused by CLN8 Dysfunction

Authors
Licitra, R., Della Vecchia, S., Santucci, L., Vivarelli, R., Bernardi, S., Santorelli, F.M., Marchese, M.
ID
ZDB-PUB-250111-3
Date
2025
Source
Cells   14(1): (Journal)
Registered Authors
Santorelli, Filippo Maria
Keywords
CLN8, behavior, dietary treatment, neuronal ceroid lipofuscinoses, translational medicine, trehalose, zebrafish
MeSH Terms
  • Disease Models, Animal
  • Zebrafish*
  • Anxiety/drug therapy
  • Neuronal Ceroid-Lipofuscinoses*/drug therapy
  • Neuronal Ceroid-Lipofuscinoses*/genetics
  • Social Behavior
  • Animals
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism
  • Locomotion/drug effects
  • Emotions/drug effects
  • Trehalose*/pharmacology
  • Trehalose*/therapeutic use
  • Behavior, Animal/drug effects
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
39791756 Full text @ Cells
Abstract
CLN8 and other neuronal ceroid lipofuscinoses (NCLs) often lead to cognitive decline, emotional disturbances, and social deficits, worsening with disease progression. Disrupted lysosomal pH, impaired autophagy, and defective dendritic arborization contribute to these symptoms. Using a cln8-/- zebrafish model, we identified significant impairments in locomotion, anxiety, and aggression, along with subtle deficits in social interactions, positioning zebrafish as a useful model for therapeutic studies in NCL. Our findings show that trehalose, an autophagy enhancer, ameliorates anxiety, and modestly improves social behavior and predator avoidance in mutant zebrafish. This finding aligns animal models with clinical reports suggestive of behavioral improvements in NCL patients. Trehalose holds promise as a therapeutic agent for CLN8, warranting further research into its neuroprotective mechanisms and clinical applications.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping