Increased anxiety-related behavior in a zebrafish model of Tuberous sclerosis complex recapitulated human symptoms of the disease

• Autorzy: Kedra M.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder, caused by mutations inactivating genes for proteins hamartin (TSC1) and tuberin (TSC2) and subsequent overactivation of mTORC1. TSC manifests itself by the presence of hamartomas in various organs, although epilepsy is the most influential in mortality. Not only neurological symptoms but also neuropsychiatric manifestations affect TSC patients, which are gathered by the name TSC-associated Neuropsychiatric Disorders (TANDs). The most common disorders are autism spectrum disorder (25‑50%), intellectual disability (30‑50%), and anxiety (30‑60%). METHOD(S): In our study we used tsc2vu242 zebrafish mutant line in which a truncating mutation in tsc2 gene led to lack of Tsc2 protein. We performed three types of behavioral test towards anxiety: Response to Sudden Light Changes, New Environment Exploration, and the Light preference test. We also measured cortisol levels in 5 dpf tsc2vu242 larvae. RESULTS: In response to the Sudden Light Changes test, tsc2vu242/vu242 mutant fish exhibited stronger freezing and hyperactivity behavior between dark and light phases compared to tsc2+/+ fish, which indicates increased anxiety. In the New Environment Exploration test, tsc2vu242/vu242 mutant fish spent less time exploring the central area of the plate compared to their sibling of other genotypes, choosing safe areas near the edges. Only in the Light Preference test, tsc2vu242/242 fish presented impaired phototaxis, preferring the dark compartment, while tsc2+/+ controls show clear positive phototaxis. Elevated cortisol levels in tsc2vu242/vu242 mutants further confirmed increased anxiety. CONCLUSIONS: We show that tsc2vu242/vu242 fish exhibit increased anxiety-related behavior compared with tsc2+/+ fish, also on the stress hormone level. The Light Preference test points to intellectual disability in the tsc2vu242/vu242 mutant. These results reflect the human phenotype of TANDs.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2019
• Tom: 79
• Numer: Suppl.1
• Opis fizyczny: p.XLVII

Twórcy

autor

Kedra M.

• International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland