The medial prefrontal cortex (mPFC) is implicated in processing sensory-discriminative and affective pain. Nonetheless, the underlying mechanisms are poorly understood. Here we demonstrate a role for excitatory neurons in the prelimbic cortex (PL), a sub-region of mPFC, in the regulation of pain sensation and anxiety-like behaviours. Using a chronic inflammatory pain model, we show that lesion of the PL contralateral but not ipsilateral to the inflamed paw attenuates hyperalgesia and anxiety-like behaviours in rats. Optogenetic activation of contralateral PL excitatory neurons exerts analgesic and anxiolytic effects in mice subjected to chronic pain, whereas inhibition is anxiogenic in naive mice. The intrinsic excitability of contralateral PL excitatory neurons is decreased in chronic pain rats; knocking down cyclin-dependent kinase 5 reverses this deactivation and alleviates behavioural impairments. Together, our findings provide novel insights into the role of PL excitatory neurons in the regulation of sensory and affective pain.

During brain development, the correct migration of newborn neurons is one of the determinants of circuit formation, and neuronal migration defects may lead to neurological and psychiatric disorders. The molecular mechanisms underlying neuronal migration and related disorders are poorly understood. Here, we report that Chromodomain Y-like (CDYL) is critical for neuronal migration in mice. Knocking down CDYL caused neuronal migration defects and disrupted both mobility and multipolar-to-bipolar transition of migrating neurons. We find that CDYL regulates neuronal migration by transcriptionally repressing RhoA. In addition, CDYL deficiency increased the excitability of cortical pyramidal neurons and the susceptibility of mice to convulsant-induced seizures. These results demonstrate that CDYL is a regulator of neuronal migration and shed light on the pathogenesis of seizure-related neurodevelopmental disorders.

BackgroundThe gut bacteria of tephritid fruit flies play prominent roles in nutrition, reproduction, maintenance and ecological adaptations of the host. Here, we adopted an approach based on direct observation of symbiotic or axenic flies feeding on dishes seeded with drops of full diet (containing all amino acids) or full diet supplemented with bacteria at similar concentrations to explore the effects of intestinal bacteria on foraging decision and fitness of Bactrocera dorsalis.ResultsThe results show that intestinal probiotics elicit beneficial foraging decision and enhance the female reproduction fitness and survival of B. dorsalis (symbiotic and axenic), yet preferences for probiotic diets were significantly higher in axenic flies to which they responded faster compared to full diet. Moreover, females fed diet supplemented with Pantoea dispersa and Enterobacter cloacae laid more eggs but had shorter lifespan while female fed Enterococcus faecalis and Klebsiella oxytoca enriched diets lived longer but had lower fecundity compared to the positive control. Conversely, flies fed sugar diet (negative control) were not able to produce eggs, but lived longer than those from the positive control.ConclusionsThese results suggest that intestinal bacteria can drive the foraging decision in a way which promotes the reproduction and survival of B. dorsalis. Our data highlight the potentials of gut bacterial isolates to control the foraging behavior of the fly and empower the sterile insect technique (SIT) program through the mass rearing.

Background Ischemic stroke (IS) is a principal contributor to long-term disability in adults. A new cell death mediated by iron is ferroptosis, characterized by lethal aggregation of lipid peroxidation. However, a paucity of ferroptosis-related biomarkers early identify IS until now. This study investigated potential ferroptosis-related gene pair biomarkers in IS and explored their roles in immune infiltration. Results In total, we identified 6 differentially expressed ferroptosis-related genes (DEFRGs) in the metadata cohort. Of these genes, 4 DEFRGs were incorporated into the competitive endogenous RNA (ceRNA) network, including 78 lncRNA-miRNA and 16 miRNA-mRNA interactions. Based on relative expression values of DEFRGs, we constructed gene pairs. An integrated scheme consisting of machine learning algorithms, ceRNA network, and gene pair was proposed to screen the key DEFRG biomarkers. The receiver operating characteristic (ROC) curve witnessed that the diagnostic performance of DEFRG pair CDKN1A/JUN was superior to that of single gene. Moreover, the CIBERSORT algorithm exhibited immune infiltration landscapes: plasma cells, resting NK cells, and resting mast cells infiltrated less in IS samples than controls. Spearman correlation analysis confirmed a significant correlation between plasma cells and CDKN1A/JUN (CDKN1A: r = − 0.503, P < 0.001, JUN: r = − 0.330, P = 0.025). Conclusions Our findings suggested that CDKN1A/JUN could be a robust and promising gene-pair diagnostic biomarker for IS, regulating ferroptosis during IS progression via C9orf106/C9orf139-miR-22-3p-CDKN1A and GAS5-miR-139-5p/miR-429-JUN axes. Meanwhile, plasma cells might exert a vital interplay in IS immune microenvironment, providing an innovative insight for IS therapeutic target.