Downregulation of lncRNAs Gomafu, NONMMUT033604.2, and NONMMUT064397.2 in the hippocampus of mice with model of post-traumatic stress disorder.

OBJECTIVES: Molecular mechanisms of post-traumatic stress disorder (PTSD) development have been analysed by evaluati-ng changes in the expression level of long non-coding RNA (lncRNA) as a potential biomarker of the disease and as one of the molecular aspects associated with the disease development. METHODS: In our study, we used quantitative polymerase chain reaction (qPCR) to evaluate changes in the expression level of long non-coding RNA - Gomafu, NONMMUT033604.2, and NONMMUT064397.2 - in the hippocampus of mice that were subjected to an artificially induced middle single prolonged stress (mSPS) model of post-traumatic stress disorder. RESULTS: We found a significant reduction in the expression levels of each of the three lncRNAs tested: Gomafu in 45.4 times, NONMMUT033604.2 in 53.4 times, and NONMMUT064397.2 in 5.2 times. The results of the present study provide evidence that the mSPS model effectively induces PTSD-like behaviour in mice leading to a significant decrease in the expression level of Gomafu, NONMMUT033604.2 and NONMMUT064397.2 lncRNA in mice hippocampus. CONCLUSIONS: This data provides evidence that the three studied lncRNAs could be potential biomarkers of PTSD development.

Ca2+-Permeable AMPA Receptors Contribute to Changed Dorsal Horn Neuronal Firing and Inflammatory Pain.

The dorsal horn (DH) neurons of the spinal cord play a critical role in nociceptive input integration and processing in the central nervous system. Engaged neuronal classes and cell-specific excitability shape nociceptive computation within the DH. The DH hyperexcitability (central sensitisation) has been considered a fundamental mechanism in mediating nociceptive hypersensitivity, with the proven role of Ca2+-permeable AMPA receptors (AMPARs). However, whether and how the DH hyperexcitability relates to changes in action potential (AP) parameters in DH neurons and if Ca2+-permeable AMPARs contribute to these changes remain unknown. We examined the cell-class heterogeneity of APs generated by DH neurons in inflammatory pain conditions to address these. Inflammatory-induced peripheral hypersensitivity increased DH neuronal excitability. We found changes in the AP threshold and amplitude but not kinetics (spike waveform) in DH neurons generating sustained or initial bursts of firing patterns. In contrast, there were no changes in AP parameters in the DH neurons displaying a single spike firing pattern. Genetic knockdown of the molecular mechanism responsible for the upregulation of Ca2+-permeable AMPARs allowed the recovery of cell-specific AP changes in peripheral inflammation. Selective inhibition of Ca2+-permeable AMPARs in the spinal cord alleviated nociceptive hypersensitivity, both thermal and mechanical modalities, in animals with peripheral inflammation. Thus, Ca2+-permeable AMPARs contribute to shaping APs in DH neurons and nociceptive hypersensitivity. This may represent a neuropathological mechanism in the DH circuits, leading to aberrant signal transfer to other nociceptive pathways.