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Ablation of Nkx2.1 derived striatal interneurons results in Tourette – like phenotypes.

Camila Coll

  • CABA,
  • Argentina
  • Camila Coll ¹
  • , Juan Pablo Beccaria ¹
  • , Bárbara Yael Braz ¹
  • , Analía López Díaz ¹
  • , Juan Emilio Belforte ¹
  • , Mario Gustavo Murer ¹
  • 1 Instituto de Fiosiología y Biofísica Bernardo Houssay (IFIBIO) UBA-CONICET

Tourette Syndrome (TS) is a neurodevelopmental disorder that usually starts during childhood. Although it is characterized by motor and vocal tics, most patients also present comorbid conditions including OCD and ADHD. Pathophysiology of TS is unknown, however, there are studies showing a reduce number of PV+, nNOS+ and ChAT+ striatal interneurons (SIs) in the brain of TS patients. Previous studies have tried to reproduce TS phenotype in mice by generating an ablation of a specific type of SI, but none have shown spontaneous tics. In order to reproduce more closely the striatal changes reported, we performed a combined ablation of SIs using a Cre/loxP transgenic system to express human diphtheria toxin receptor in Nkx2.1+ cell lineage, combined with intrastriatal diphtheria toxin administration. Immunohistochemistry assays showed that lesion exclusively affected SIs. Lesioned mice not only developed abnormal involuntary movements resembling motor tics (See Beccaria et al. poster) but also behaviors reminiscent of common comorbid conditions, including an increase in stereotypies (grooming), locomotion, and spontaneous repetitive behaviors (rearing and head poking), as well as a reduction in immobility time, compared to their control littermates. These phenotypes suggest perseverative-like behaviors and hyperactivity, compatible with OCD and ADHD comorbidities. In summary, animals with ablated Nkx2.1 derived SIs develop TS-like phenotypes.