Therapeutic Potential of the Purinergic System in Major Depressive Disorder Associated with COVID-19

Abstract

Neuroinflammation is closely related to the development of depression, since the latter is caused, among other factors, by inflammatory processes, mainly related to the activation of microglia and expression of specific genes, which occurs during the neuroinflammatory process. Thus, COVID-19 is an important risk factor for the development of depression, since in addition to generating the feeling of stress, which also increases the activity of the immune system, it is also the cause of pathological processes and physiological ones that lead to the development of neuroinflammation, microglial activation, gene expression dysfunction and decreased concentration of available serotonin. That said, drugs are being used to combat COVID-19 to reduce the oxidative stress presented in the disease. Thus, tramadol and fluoxetine are highlighted as drugs used, however, although they present some positive results, such as the reduction of pro-inflammatory cytokines, they are also associated with negative effects such as dependence, pulmonary, cardiac and brain impairment. From this, the purinergic system is highlighted in the literature as a possible therapeutic target. This is because its mechanisms are related to the regulation of microglia, astrocytes and the physiology of important neurotransmitters and hormones. Added to this, there is a modulation of inflammatory activity, especially with regard to the P2X7 receptors of this system. The latter is an important target for the treatment of depression and COVID-19, since positive results were obtained through the genetic exclusion of this receptor and the use of selective antagonists. Graphical Abstract

Ferulic acid alleviates sciatica by inhibiting neuroinflammation and promoting nerve repair via the TLR4/NF‐κB pathway

“…IBA‐1 is a marker of activated microglia and macrophage. Activation of microglia and macrophage induces neuroinflammation 25 . Macrophages in the sciatic nerve had some characteristics of microglia 26 .…”

“…Activation of microglia and macrophage induces neuroinflammation. 25 Macrophages in the sciatic nerve had some characteristics of microglia. 26 Acute injury of the sciatic nerve led to a rapid infiltration of circulating monocytes, and the monocytes quickly adapted a macrophage phenotype.…”

Oxidative Stress and Inflammation Biomarkers in Postoperative Pain Modulation in Surgically Treated Patients with Laryngeal Cancer—Pilot Study

“…It was established that tramadol acts as an anti-inflammatory agent. Tramadol can suppress the cytokine storm through decreasing interleukins such as IL6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) [51,52]. Tramadol can also increase levels of the antioxidant enzymes superoxide dismutase and glutathione peroxidase and decrease the level of MDA in testicular ischemia-reperfusion injury [53].…”