Neu1 deficiency induces abnormal emotional behavior in zebrafish

Area of Science:

• Biochemistry
• Neuroscience
• Genetics

Background:

• NEU1 sialidase is crucial for lysosomal function, hydrolyzing sialic acids from glycoconjugates.
• NEU1 deficiency leads to sialidosis, a genetic disorder with physical and neurological symptoms.
• The impact of NEU1 deficiency on emotional behaviors remains largely unexplored.

Purpose of the Study:

• To investigate the behavioral and emotional effects of NEU1 deficiency in a zebrafish model.
• To explore the underlying molecular mechanisms related to NEU1 deficiency and emotional dysregulation.

Main Methods:

• Behavioral analyses were performed on NEU1-knockout (Neu1-KO) zebrafish and wild-type (WT) zebrafish.
• Tests included shoaling, aggression, social interaction (mirror and 3-chamber tests), and black-white preference.
• Gene expression analysis of the hypothalamic-pituitary-adrenal axis and lysosomal markers was conducted.

Main Results:

• Neu1-KO zebrafish exhibited reduced shoaling, decreased aggression, and altered social interactions compared to WT.
• Neu1-KO zebrafish showed abnormal preferences in spatial and novelty tests, indicating anxiety-like behavior.
• Molecular analysis revealed downregulation of anxiety-related genes and upregulation of lysosomal exocytosis markers in Neu1-KO brains.

Conclusions:

• NEU1 deficiency in zebrafish results in significant alterations in emotional and social behaviors.
• These behavioral changes may be linked to neuronal dysfunction driven by lysosomal exocytosis and sphingoglycolipid accumulation.
• Zebrafish models offer valuable insights into the neurological and emotional consequences of NEU1 deficiency.