Two distinct evolutionary conserved neural degeneration pathways characterized in a colonial chordate

Area of Science:

• Neuroscience
• Developmental Biology
• Evolutionary Biology

Background:

• Colonial tunicates possess multiple brains during their colonial phase.
• Previous studies documented neurogenesis and neurodegeneration cycles but lacked cellular and molecular detail.
• The relationship between brain morphology, behavior, and these neural processes in adult tunicates was unknown.

Purpose of the Study:

• Introduce *Botryllus schlosseri* as a model for neurogenesis, neural degeneration, and evolutionary neuroscience.
• Investigate cellular and molecular changes during tunicate neurodegeneration.
• Explore the link between aging, neural processes, and behavior in tunicates.

Main Methods:

• Comparative analysis of neuron counts and gene expression in tunicate brains.
• Assessment of behavioral responses in young versus aged colonies.
• Examination of neural changes during weekly colony budding (asexual reproduction).

Main Results:

• Decreased neuron numbers during budding correlated with reduced behavior and altered expression of 73 mammalian homologous genes linked to neurodegeneration.
• Older colonies (∼20 years) showed fewer neurons, reduced behavior, and altered expression of 148 neurodegeneration-associated genes compared to young colonies.
• Identified two distinct neurodegenerative pathways, with 35 overlapping differentially expressed genes across both timescales.

Conclusions:

• *Botryllus schlosseri* provides a novel model for studying aging, neural regeneration, and degeneration.
• The findings offer mechanistic insights into the evolution of nervous system function and neurodegenerative diseases.
• This tunicate's evolutionary position offers a unique perspective on vertebrate neural evolution.