Abstract
Fragile X-related protein 1 (FXR1) is a member of the fragile X family of RNA-binding proteins, which regulates a number of neurological and neuropsychiatric disorders such as fragile X syndrome, and is expected as a novel therapeutic target for some psychiatric diseases. However, it is unknown how FXR1 changes and functions in post-traumatic stress disorder (PTSD), a common mental disorder related to trauma and stressor. In this study, we characterized the expression pattern of FXR1 in the pathophysiological process of PTSD and further investigated the possible mechanism underlying these changes by finding an upstream regulator, namely miRNA-132 (miR-132). Furthermore, we verified whether miR-132 silence had an effect on the PTSD-like behaviors of single prolonged stress (SPS) rats through open field test, forced swimming test, and water maze test. At last, we examined the expression levels of PSD95 and synapsin I in the hippocampus, which was one of the key brain regions associated with PTSD. We showed that the levels of FXR1 and fragile X mental retardation protein (FMRP), an autosomal homolog of FXR1, were decreased in the hippocampus of PTSD rats, but the levels of PSD95 and synapsin I were increased, which could be reversed by downregulation of miR-132. The results revealed that miR-132 could modulate PTSD-like behaviors in rats following SPS through regulating FXR1 and FMRP.
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This work was supported by grants from the Natural Science Foundation of Liaoning Province, China (Nos. 201602825 and 20170541011) and the Educational Commission of Liaoning Province, China (QN2019024).
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LT designed the research and revised the manuscript. PYN and CHF performed the experiments and analyzed the data. LLJ contributed to part of immunofluorescence staining and drafted the manuscript. JBP and ZYW provided technical supports as experts in molecular biology. All authors reviewed and approved the final manuscript.
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All experiments were conducted in accordance with the NIH guidelines using approved protocols from the Animal Care and Use Committee (China Medical University). All efforts were made to minimize the number of mice used and their suffering.
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Nie, PY., Ji, LL., Fu, CH. et al. miR-132 Regulates PTSD-like Behaviors in Rats Following Single-Prolonged Stress Through Fragile X-Related Protein 1. Cell Mol Neurobiol 41, 327–340 (2021). https://doi.org/10.1007/s10571-020-00854-x
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DOI: https://doi.org/10.1007/s10571-020-00854-x