Topic: PsychologyDevelopment

Last updated: April 8, 2019

Fragile X is the type of inherited human mental retardation caused by a trinucleotide repeat expansion in the X-linked FMR1 gene. FMR1 gene prevents expression of the encoded protein that is called fragile X mental retardation protein (FMRP). FMRP can be found in synapses where it links with mRNA and polyribosomes. Based on the mGluR theory of fragile X syndrome, this patholoogy due to the loss of the fragile X mental retardation protein (FRMP), which leads to the development of long-term depression (LTD).

LTD takes place when the group 1 mGluRs is activated. This activation usually occurs in response to strong activity and triggers long-term plasticity of synaptic transmission in the brain regions like hippocampus or neocortex. The theory suggests that the group 1 mGluRs and the fragile X mental retardation protein FMRP act in opposition to one another, where FMRP carries out repression of the mRNAs and mGluRs activate the mRNAs. The scientists explain that the over-active signaling by group 1 mGluRs can be an underlyning cause of many symptoms present in people with fragile X not only exaggerated LTD or decreased synaptic development.

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They believe that psychiatric and neurological aspects of fragile X syndrome are a result of exaggerated responses to mGluR1/5 activation due to the two findings:a) in response to activation of mGluR1/5 proteins are being synthesized near synapses in various brain regions, where they participate in diverse neuronal functions;b) FMRP negatively regulates responses triggered by mGluR-stimulated protein synthesis;Thus, the defficiency of FMRP leads to a dysregulated synthesis of molecules essential for normal functioning of synapses, based on the results of the experiments conducted with mouse hippocampus. It also increases LTD in mouse hippocampus, which confrms the function of FMRP as a repressor of translation of specific mRNAs.


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