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

• Published in: Cellular and molecular life sciences : CMLS 2023-12, Vol.80 (12), p.370-370, Article 370
• Main Authors: Fructuoso, Marta, Fernández-Blanco, Álvaro, Gallego-Román, Ana, Sierra, Cèsar, de Lagrán, María Martínez, Lorenzon, Nicola, De Toma, Ilario, Langohr, Klaus, Martín-García, Elena, Maldonado, Rafael, Dairou, Julien, Janel, Nathalie, Dierssen, Mara
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain research; Carbohydrates; Cell Biology; Diet; Disease Models, Animal; Dopamine receptors; Down syndrome; Down Syndrome - genetics; Down's syndrome; Eating behavior; Energy; Energy utilization; Food; Food preferences; Hedonic response; Humans; Hyperphagia - genetics; Impulsive behavior; Laboratory animals; Life Sciences; Male; Males; Meal pattern; Medical research; Mice; Neurosciences; Nucleus accumbens; Obesity; Obesity - genetics; Original; Original Article; Pattern analysis; Prefrontal Cortex; Proteins; Quinine; Research parks; Trisomy
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-023-05009-x

Individuals with Down syndrome (DS) have a higher prevalence of obesity compared to the general population. Conventionally, this has been attributed to endocrine issues and lack of exercise. However, deficits in neural reward responses and dopaminergic disturbances in DS may be contributing factors. To investigate this, we focused on a mouse model (Ts65Dn) bearing some triplicated genes homologous to trisomy 21. Through detailed meal pattern analysis in male Ts65Dn mice, we observed an increased preference for energy-dense food, pointing towards a potential “hedonic” overeating behavior. Moreover, trisomic mice exhibited higher scores in compulsivity and inflexibility tests when limited access to energy-dense food and quinine hydrochloride adulteration were introduced, compared to euploid controls. Interestingly, when we activated prelimbic-to-nucleus accumbens projections in Ts65Dn male mice using a chemogenetic approach, impulsive and compulsive behaviors significantly decreased, shedding light on a promising intervention avenue. Our findings uncover a novel mechanism behind the vulnerability to overeating and offer potential new pathways for tackling obesity through innovative interventions.