Abstract
BackgroundFMRP is a selective mRNA-binding protein that regulates protein synthesis at synapses, and its loss may lead to the impairment of trace fear memory. Previously, we found that FMRP levels in the hippocampus of rats with post-traumatic stress disorder (PTSD) were decreased. However, the mechanism underlying these changes remains unclear.MethodsForty-eight male Sprague-Dawley rats were randomly divided into four groups. The experimental groups were treated with the single-prolonged stress (SPS) procedure and injected with a lentivirus-mediated inhibitor of miR-142-5p. Behavior test as well as morphology and molecular biology experiments were performed to detect the effect of miR-142 downregulation on PTSD, which was further verified by in vitro experiments.ResultsWe found that silence of miRNA-142 (miR-142), an upstream regulator of FMRP, could alleviate PTSD-like behaviors of rats exposed to the SPS paradigm. MiR-142 silence not only decreased the levels of proinflammatory mediators, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α, but also increased the expressive levels of synaptic proteins including PSD95 and synapsin I in the hippocampus, which was one of the key brain regions associated with PTSD. We further detected that miR-142 silence also downregulated the transportation of nuclear factor kappa-B (NF-κB) into the nuclei of neurons and might further affect the morphology of neurons.ConclusionsThe results revealed miR-142 downregulation could alleviate PTSD-like behaviors through attenuating neuroinflammation in the hippocampus of SPS rats by binding to FMRP.
Highlights
Post-traumatic stress disorder (PTSD) is one of the psychiatric disorders related to pathological fear and anxiety [1, 2]
Antisense miR-142-5p alleviated post-traumatic stress disorder (PTSD)-like behavior in rats exposed to the single-prolonged stress (SPS) procedure After administering antisense miR-142-5p delivered by LV-anti-miR-142 or LV-Control through the lateral ventricle, different behavioral tests were performed and the rats were sacrificed at different time points from other experimental procedures (Fig. 1a)
We found that the level of IL-1β, tumor necrosis factor-α (TNF-α), and IL-6 expression was significantly increased in the hippocampus of rats exposed to the SPS procedure compared to the levels in the control group (Fig. 5a–f)
Summary
Post-traumatic stress disorder (PTSD) is one of the psychiatric disorders related to pathological fear and anxiety [1, 2]. Neuroinflammation is characterized by the activation of glial cells (mainly astrocytes and microglia), which release various soluble factors, including cytokines, reactive oxygen species (ROS) and reactive nitrogen species (RNS), and lipid metabolites. Most of these glia-derived factors are proinflammatory and neurotoxic and are deleterious to neurons [9, 10].
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