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Issue Date: 20-Feb-2017
Authors: Heiss, Kathrin
Title: Role of pentazocine in an in vitro model of hypoxia/reoxygenation
Abstract: Experimental research is making considerable efforts to understand the rules that regulate the balance between toxic and protective brain innate immunity. Sigma-1 receptor is expressed in both neurons and glia is a unique class of intracellular proteins and is involved in neurodegeneration. Our aim was to evaluate the biological effects of sigma-1 selective ligands, and bifunctional sigma-1 selective ligands conjugated with lipoil function in microglia following hypoxia/reoxygenation condition. BV2 cells were exposed to 3 hours of hypoxia and 24h of reoxygenation. Cells were treated with sigma-1 agonist (+)-Pentazocine, various bifunctional sigma-1 agonists conjugated with lipoil function and with lipoic acid alone. We assessed cell viability, apoptosis, reactive oxygen species (ROS) formation, mitochondria membrane potential, and total thiol groups content (GSH). Our results showed that 24h of reoxygenation resulted in a significant decrease of cell viability and increase in apoptosis when compared to control. No significant effect of (+)Pentazocine and tested compounds was observed on cell viability following 24h of reoxygenation. Furthermore, all treatments resulted in a significant decrease of ROS formation when compared to untreated cells. Finally, pharmacological treatments restored mitochondrial membrane potential when compared to the untreated group. Consistently with these results we also showed that GSH content was restored following pharmacological treatments. Our results showed that newly synthetized bifunctional sigma-1 compounds exhibited significant antioxidant activity and induce apoptosis in activated microglia thus providing a new tool for effective manipulation of brain inflammation, with the specific aim of favoring its protective arm and boosting innate neuroprotective mechanisms 6 GENERAL INTRODUCTION MICROGLIA The concept of microglia was introduced by Pio del Rio-Hortega as a defined cellular element
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