Astrocyte Elevated Gene-1 (AEG-1) Deletion Selectively Enhances the Antinociceptive Effects of Morphine

Background: Opioids are a class of drugs that are utilized in clinical settings to alleviate acute and chronic pain, but can often lead to development of tolerance, addiction and overdose following prolonged usage. Opioids such as morphine function by activating endogenous µ opioid receptors, which are located in various tissues throughout the body. Astrocyte Elevated Gene-1 (AEG-1) is a multifunctional protein that regulates inflammation, myeloid cell activity and lipid metabolism. Studies have shown interactions and overlaps in cellular signaling between the inflammatory/immune responses and the endogenous opioid system which could suggest a role for AEG-1 in opioids effects. Our goal is to investigate the role of AEG-1 in morphine mediated pharmacological effects including analgesia. Methods: Adult AEG-1 global knockout (KO) and wild-type (WT) male and female mice (C57BL/6J background) were utilized to assess morphine-induced thermal antinociception (The tail immersion assay test), hyperlocomotion, gastrointestinal (GI) transit inhibition, and tolerance. GI transit was assessed via charcoal transit assay. Locomotor boxes were used to assess spontaneous activity in mice. Results: AEG-1 KO mice displayed increased thermal antinociception following acute and repeated morphine administration compared to their WT counterparts. Pretreatment with naloxone blocked the enhancement of morphine thermal antinociception in AEG-1 KO mice. In addition, chronic morphine treated AEG-1 KO mice displayed reduced morphine tolerance development compared to their WT counterparts. No significant differences in morphine-induced hyperlocomotion or GI transit inhibition were observed between AEG-1 KO and WT mice. Conclusions: Our data suggest that AEG-1 deletion enhances the antinociceptive effects of morphine and reduces tolerance to chronic morphine treatment. However, AEG-1 deletion does not impact morphine-induced locomotor activity of GI transit inhibition. Overall, our results suggest that AEG-1 may function as a modulator of the endogenous opioid system.https://scholarscompass.vcu.edu/uresposters/1413/thumbnail.jp

Dietary intake of Spirulina platensis alters HSP70 gene expression profiles in the brain of rats in an experimental model of mixed stress

Spirulina platensis has gradually gained more attention for its therapeutic, antioxidant, and anti-inflammatory potential worldwide. However, the current molecular knowledge about the effects of spirulina on stress-related genes is rather limited. The effects of dietary intake of spirulina on the HSP70 gene expression were assessed in a controlled in vivo experimental design. Moreover, alterations in serum corticosterone levels, IL-2, IL-4, IFN-gamma, triglyceride, ALT, AST, relative gene expression values, and the correlations between them were evaluated. A total of 36 rats were divided into four groups: control group, stress-only group, spirulina group, and spirulina+stress group. To control the dose administration, S. platensis was applied by a gastric gavage in stress groups. Crowded environment stress and hosting alone stress were applied to the stress-only group and spirulina + stress group. RNA was extracted from brain samples using TRlpure and the relative gene expression assessment was performed using Roche-LightCycler-480-II real-time PCR-System. Gene expression values were remarkably different among the four experimental groups. The differences between stress-only and the spirulina groups were statistically significant (P<0.05). The correlation between the HSP70 gene expression and the IFN-gamma was found to be statistically significant (P<0.05; r=0.50). Results indicate a novel effect of spirulina on the HSP70 expression related to the stress-response. Data presented in this study may be useful for further studies to define not only the molecular genetic aspects through dietary S. platensis but also the effects of spirulina on stress-response and animal welfare.YoK (Council of Higher Education) 100/200 Doctoral Research Fellowship Programme; TuBTAK (The Scientific and Technological Research Council of Turkey)The data on some parts of the research has been presented as an oral presentation at the 2nd International Eurasian Conference on Science, Engineering and Technology (EurasianSciEnTech 2020), Gaziantep, Turkey. Eda Koseli was supported by YoK (Council of Higher Education) 100/200 Doctoral Research Fellowship Programme and TuBTAK (The Scientific and Technological Research Council of Turkey) 2211-C (National Ph.D. Scholarship Programme in the Priority Fields in Science and Technology). The authors are grateful to Dr Ozge Ardicli for her support