Altered Behavioral Performance and Live Imaging of Circuit-Specific Neural Deficiencies in a Zebrafish Model for Psychomotor Retardation

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In a wide range of brain disorders, mutations in specific genes cause alterations in the development and function of neural circuits that ultimately affect behavior. A major challenge is to uncover the mechanism and provide treatment which is capable of preventing brain damage. Allan-Herndon-Dudley syndrome (AHDS) is a severe psychomotor retardation characterized by intellectual disabilities, neurological impairment and abnormal thyroid hormone (TH) levels. Mutations in the TH transporter MCT8 are associated with AHDS. Mice that lack the MCT8 protein exhibited impaired TH levels, as is the case in human patients; however, they lack neurological defects. Here, we generated an mct8 mutant (mct8−/−) zebrafish, which exhibited neurological and behavioral deficiencies and mimics pathological conditions of AHDS patients. The zebrafish is a simple transparent vertebrate and its nervous system is conserved with mammals. Time-lapse live imaging of single axons and synapses, and video-tracking of behavior revealed deficiencies in neural circuit assembly, which are associated with disturbed sleep and altered locomotor activity. In addition, since the mct8−/ −⁠ larvae provides a highthroughput platform for testing therapeutic drugs, we showed that TH analogs can recover neurological deficiencies in an animal model for psychomotor retardation.

Vyšlo v časopise: Altered Behavioral Performance and Live Imaging of Circuit-Specific Neural Deficiencies in a Zebrafish Model for Psychomotor Retardation. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004615
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004615

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