Neuroinflammation involves glia activation, releasing of inflammatory mediators such as cytokines and chemokines, and formation of reactive oxygen and nitrogen species. It plays a central role in many neurodegenerative diases processes such as Alzheimer’s disease, Parkinson’s disease, dementia. Estrogen deprivation, commonly associated with aging, loss of learning and memory skills in postmenopausal women and Alzheimer’s disease. In this study, we studied effects of 17-ßestradiol on kynunerine pathway and NK-kB gene expression in neuroinflammation. According to our results, estrogen increased expression of kynunerinase gene and decreased IDO-1 gene expression after TNF-alpha incubation in differentiated SH-SY5Y cells. However, it did not change NF-kB gene expression.
The neuroinflammation; is a response that includes all the cells, including the central nervous system, neurons, macroglia and microglia, and can be a negative factor in acute and chronic brain disorders in connection with the brain. Cellular and molecular immunological components such as cytokines, reactive oxygen and nitrogen species and glial cells; Activation of microglia and astrocytes causes neuroinflammation. Neuroinflammation plays an important role in many neurodegenerative diseases such as multiple sclerosis (MS), Alzheimer’s disease (AD), ALS, Parkinson’s disease and autism (Carson, Doose, Melchior, Schmid, & Ploix, 2006). In order to activate complex neuroinflammatory pathways and microglia; factors such as genetic, environmental, age and past experiences have significant effects(Hof & Mobbs, 2009). There are many potential mechanisms that estrogen can influence the symptoms of Alzheimer’s risk and phenotype (Rosini, Simoni, Caporaso, & Minarini, 2016). The degeneration of cholinergic neurons and accumulation of amyloid β plaques cause the disease to progress gradually (Chen et al., 2016) (Shamim & Laskowski, 2017). Oxidative stress is thought to be one of the main causes of Alzheimer’s disease. ROS induces neuroinflammation by stimulating gene transcription by the release of cytokines such as pro-inflammatory TNF-α (Akbar et al., 2016)(Morales et al., 2014).
The levels of TNF-α in healthy people’s brain are low and their physiological role is uncertain. An increase in TNF-α levels is observed in chronic inflammation and inflammation plays a leading role, especially in the early stages of the disease. Proinflammatory mediators and nuclear transcription factor (NF-B) are directly or indirectly involved in the production of a large number of pro-inflammatory cytokines such as TNF-α. NF-κB is a key control role in inflammation and is an important target for anti-inflammatory therapeutic interventions (Ivanenkov, Balakin, & Lavrovsky, 2011). In the TNF-α mediated inflammation model, it was observed that ER activation and 17-β estradiol inhibited nuclear translocation of NF-kB, (Ghisletti, Meda, Maggi, & Vegeto, 2005).