👤 Ian De Belle

Physical exercise is widely recognized for reducing neuropathic pain. However, the interaction between the immune and opioidergic systems in supraspinal structures is still not fully understood. To evaluate the impact of opioid receptor blockade on the effects of low-intensity exercise on the sensory, cognitive, and emotional aspects of neuropathic pain after sciatic nerve injury. Male Swiss mice (2 months old) were submitted to sciatic nerve crush and divided into sedentary or exercised groups. The exercised groups performed treadmill running for two weeks, with or without naloxone pre-treatment to block opioid receptors. Sensory responses were assessed using the von Frey test, while cognitive and emotional-like behaviors were evaluated through the Mechanical Conflict-Avoidance System (MCAS) and open field test, respectively. Cytokine levels (IL-4, IL-10) and brain-derived neurotrophic factor (BDNF) were quantified in the brainstem and prefrontal cortex by ELISA. Exercise reduced mechanical hypersensitivity and improved performance in cognitive and exploratory tasks. These effects were prevented by naloxone administration. Exercise also increased IL-4, IL-10, and BDNF levels in supraspinal regions, while naloxone reversed these changes, indicating the involvement of μ-opioid receptors in exercise-induced immunomodulation. Low-intensity exercise promotes analgesia and neuroimmune regulation in neuropathic pain through supraspinal μ-opioid receptor activation. The blockade of these receptors abolishes the beneficial effects of exercise, reinforcing the interaction between opioidergic and immune systems in pain modulation. Show less

DNA microarrays of promoter sequences have been developed in order to identify the profile of genes bound and activated by DNA regulatory proteins such as the transcription factors c-Jun and ATF2 as well as DNA-modifying methylases. The arrays contain 3083 unique human promoter sequences from +500 to -1000 nts from the transcription start site. Cisplatin-induced DNA damage rapidly leads to specific activation of the Jun kinase pathway leading to increased phosphorylation of c-Jun and ATF2-DNA complexes at hundreds of sites within 3 hours. Using three statistical criteria, approximately 269 most commonly phosphorylated c-Jun/ATF2-DNA complexes were identified and representative cases were verified by qPCR measurement of ChIP-captured DNA. Expression was correlated at the mRNA and protein levels. The largest functional cohort was 24 genes of known DNA repair function, most of which exhibited increased protein expression indicated coordinate gene regulation. In addition, cell lines of prostate cancer exhibit stable methylation or copy number changes that reflect the alterations of the corresponding primary tumors. 504 (18.5%) promoters showed differential hybridization between immortalized control prostate epithelial and cancer cell lines. Among candidate hypermethylated genes in cancer-derived lines, eight had previously been observed in prostate cancer, and 13 were previously determined methylation targets in other cancers. The vast majority of genes that appear to be both differentially methylated and differentially regulated between prostate epithelial and cancer cell lines are novel methylation targets, including PAK6, RAD50, TLX3, PIR51, MAP2K5, INSR, FBN1, GG2-1, representing a rich new source of candidate genes to study the role of DNA methylation in prostate tumors. Earlier studies using prototype promoter arrays examine approximately 7% of the proximal regulatory sequences while the current gene regulatory events surveyed here occur on a large scale and may rapidly effect the coordinated expression of a large number of genes. Show less