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Impaired commissural tract fasciculation is related to increased epileptogenesis and anxiety in the zebrafish model of tuberous sclerosis complex

100%

Zmorzynska J.

Acta Neurobiologiae Experimentalis

2019

tom 79

nr Suppl.1

Tuberous sclerosis complex (TSC) is an autosomal dominant disease caused by mutations in genes encoding for TSC1 or TSC2. These proteins form a complex that inhibits mTORC1 signaling, which activates multiple molecular pathways leading to growth and differentiation in neurons. Lack of TSC1‑TSC2 functional complex due to mutations results in mTORC1 overactivation and neurodevelopmental syndromes such as epilepsy, intellectual disability, or autism spectrum disorder. To investigate the mechanisms underlying TSC disease, we use zebrafish mutant TSC2vu242. We examined TSCvu242 fish using various behavioral tests and by live brain imaging with light‑sheet microscopy. We confirmed that homozygotic TSC2vu242 mutants were lethal at the early larval stage, underscoring the importance of maintaining proper mTORC1 signaling. Also, TSC2vu242 brains showed increased activation of the mTORC1 pathway and white matter thinning. We discovered improper axon development and axonal tract fasciculation, together with changes in the expression of genes involved in axon guidance. Live imaging showed neuronal hyperexcitability in the brain and epileptogenesis in the early development of the Tsc2‑deficient fish. Together with decreased locomotion of TSC2vu242 mutants, these results suggest non‑motor seizures. We also examined fish by multiple anxiety-testing behavioral tests and found an increase in anxiety in mutant fish. Moreover, we could rescue anxiety-related behavior and white matter thinning in the TSC2vu242 mutants using the same drug. These results suggest that white matter disruption contributes to neurodevelopmental syndromes such as anxiety and epilepsy in the fish model of TSC disease

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Okiem ryby - nowe spojrzenie na rozwój sieci neuronalnych i choroby neurorozwojowe

51%

Kedra M., Jaworski J., Zmorzynska J.

Wszechświat

2016

tom 117

nr 10-12

Ograniczanie wyników

1 Acta Neurobiologiae Experimentalis

1 Wszechświat

2 Zmorzynska J.

1 Jaworski J.

1 Kedra M.

1 2019

1 2016

Wyniki wyszukiwania

Impaired commissural tract fasciculation is related to increased epileptogenesis and anxiety in the zebrafish model of tuberous sclerosis complex

Okiem ryby - nowe spojrzenie na rozwój sieci neuronalnych i choroby neurorozwojowe