Abstract
Fragile X Syndrome is a monogenic disorder that reflects a loss of Fragile X Mental Retardation Protein (FMRP) that is needed to regulate translation of proteins important to circuit development and plasticity. A complete loss of FMRP is the leading monogenic cause of Autism Spectrum Disorders (ASD). Mossy fiber inputs to cerebellar granule cells exhibit long-term potentiation (LTP) to process sensory information to the cerebellum. Here we find that LTP of mossy fiber input is lost in FMRP KO mice. To counter this loss, we reintroduced an FMRP N-terminal fragment conjugated to a tat peptide (FMRP-N-tat) by tail vein injection. This action promoted transport of FMRP(1–297) across the blood–brain barrier to distribute widely across the brain within 30 min and rescued LTP at the mossy fiber-granule cell synapse. These findings are important in revealing that tat-conjugated FMRP fragments can be used as a therapeutic tool to restore synaptic plasticity and reduce symptoms of Fragile X Syndrome.
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Zhan, X., Turner, R.W. (2023). Restoring a Loss of Mossy Fiber Plasticity in a Model of Fragile X Syndrome. In: Gruol, D.L., Koibuchi, N., Manto, M., Molinari, M., Schmahmann, J.D., Shen, Y. (eds) Essentials of Cerebellum and Cerebellar Disorders. Springer, Cham. https://doi.org/10.1007/978-3-031-15070-8_48
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DOI: https://doi.org/10.1007/978-3-031-15070-8_48
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