Exploring the link between hedonic overeating and prefrontal cortex dysfunction in the Ts65Dn trisomic mouse model.

Area of Science:

• Neuroscience
• Genetics
• Obesity Research

Background:

• Individuals with Down syndrome (DS) exhibit a higher prevalence of obesity.
• Traditional explanations focus on endocrine factors and reduced physical activity.
• Emerging evidence suggests neural reward pathway deficits and dopaminergic disturbances may contribute to obesity in DS.

Purpose of the Study:

• To investigate the role of neural reward system dysfunction in obesity within a mouse model of Down syndrome (Ts65Dn).
• To explore potential therapeutic interventions targeting brain reward pathways for managing obesity in DS.

Main Methods:

• Utilized the Ts65Dn mouse model, which carries homologous genes to human trisomy 21.
• Conducted detailed meal pattern analysis to assess feeding behavior.
• Employed behavioral tests including limited access to palatable food and quinine adulteration to evaluate compulsivity and inflexibility.
• Used chemogenetics to activate prelimbic-to-nucleus accumbens projections in male Ts65Dn mice.

Main Results:

• Ts65Dn mice showed a preference for energy-dense foods, indicating hedonic overeating.
• Trisomic mice displayed increased compulsive and inflexible behaviors when faced with food restrictions or adulteration.
• Chemogenetic activation of prelimbic-to-nucleus accumbens pathways significantly reduced impulsive and compulsive eating behaviors in Ts65Dn mice.

Conclusions:

• Neural reward pathway deficits and dopaminergic disturbances are implicated in the increased obesity risk in Down syndrome.
• Hedonic overeating and compulsive food-seeking behaviors are key factors contributing to obesity in this population.
• Targeting prelimbic-to-nucleus accumbens pathways presents a promising therapeutic strategy for addressing obesity in Down syndrome.