Trehalose Ameliorates Zebrafish Emotional and Social Deficits Caused by CLN8 Dysfunction

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.