Journal of molecular neuroscience : MN
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In an effort to understand the underlying mechanisms of cancer-induced bone pain, we investigated the presence of two protease-activated receptors, protease-activated receptor 2 (PAR2), and protease-activated receptor 4 (PAR4), in dorsal root ganglia (DRGs) neurons in an animal model of bone cancer pain. Female Wistar rats were randomized into three groups: tumor-bearing animals killed after 14 days (D14) and tumor-bearing animals killed after 21 days (D21) group and a sham operation group. After establishment of the Walker 256 carcinoma bone cancer pain model, behavioral tests were carried out to determine both the spontaneous nocifensive behavior and the paw withdrawal threshold (PWT) of mechanical and thermal hyperalgesia in these rats. ⋯ Compared to sham group, the relative mRNA and protein expression of PAR2 and PAR4 was significantly upregulated in the D14 group and D21 groups, concurrent with tumor growth and proliferation. In addition, we identified the co-expression of PAR2 and PAR4 in the DRG neurons. The upregulation of mRNA and protein levels as well as the co-localization of PAR2 and PAR4 in DRG neurons suggests their novel involvement in the development and maintenance of bone cancer pain.
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Chronic sleep fragmentation (SF), common in patients with sleep apnea, correlates with the development of obesity. We hypothesized that SF differentially affects neurobehavior in lean wild-type (WT) and obese pan-leptin receptor knockout (POKO) mice fed the same normal diet. First, we established an SF paradigm by interrupting sleep every 2 min during the inactive light span. ⋯ Both the POKO mutation and SF resulted in reduced physical activity and increased anxiety, but there was no additive effect of these two factors. Overall, SF and the POKO mutation differentially regulate mouse behavior. The results suggest that obesity can blunt neurobehavioral responses to SF.
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The present study was designed to investigate the effect of licofelone-a dual cyclooxygenase/5-lipoxygenase (COX/5-LOX) inhibitor in intracerebroventricular streptozotocin (ICV-STZ)-induced cognitive deficit and biochemical abnormalities in rats. ICV-STZ is a widely used model of sporadic Alzheimer's disease. In this study, STZ was administered intracerebroventricular (i.c.v.)-bilaterally 3 mg/kg in rats. ⋯ In addition, licofelone attenuated STZ-induced oxidative stress and elevated cytokine levels. The cognitive enhancement following licofelone administration in STZ rats may be due to its ability to restore cholinergic functions or its antioxidant activity. These observed results suggest the therapeutic potential of dual COX/5-LOX inhibitors in neurodegenerative disorders associated with oxidative stress and cognitive impairment.