ESE1 is Associated with Neuronal Apoptosis in Lipopolysaccharide Induced Neuroinflammation

Abstract

Neuronal apoptosis induced by the over-activation of microglia during neuroinflammation contributes to the pathology of central nervous system (CNS) degenerative diseases. ESE1 regulates apoptosis of intestinal epithelial cells in ulcerative colitis via accelerating NF-κB activation. NF-κB activation participates in neuronal apoptosis. However, the expression and functions of ESE1 in neuronal apoptosis during CNS inflammatory response remain unclear. In present study, ESE1 expression significantly increased in cerebral cortex after lipopolysaccharide (LPS) intracerebroventricular injection. Immunofluorescence staining indicated that ESE1 was located in neurons. Furthermore, there was a concomitant up-regulation of apoptotic markers including active caspase-3, BAX and decreased expression of anti-apoptosis protein Bcl-2. In vitro, ESE1 depletion in cortical primary neurons inhibited active caspase-3 and BAX expression as well as lactate dehydrogenase (LDH) release with up-regulation of Bcl-2, while ESE1 overexpression can exert opposite effects, indicating that ESE1 promoted neuronal apoptosis induced by LPS or LPS exposed microglia conditioned media (CM). ESE1 accelerated NF-κB activation in neurons with CM treatment. Collectively, all these data suggested that ESE1 might boost neuronal apoptosis during neuroinflammation via up-regulating NF-κB activation. These findings have implications on the potential target of ESE1 in CNS inflammation treatment.

Roflupram, a Phosphodiesterase 4 Inhibitior, Suppresses Inflammasome Activation through Autophagy in Microglial Cells

“…Here, our results were in accordance with the other findings of activated microglia-mediated neuronal apoptosis. 41,42 Notably, the alterations in the synaptic structures were observed in some of the surviving cells (Figures 6A and 7A). After incubation with activated microglial CM for 24 h, the neurites of the surviving N2a cells were shorter than that of the controls (Figures 6A and 7A).…”

“…Microglial activation and the subsequent secretion of inflammatory factors in the CNS could induce neuronal apoptosis and synaptic damage. 40,41 To examine whether the anti-inflammatory effects of ROF confer neuroprotection, CM from the microglial BV-2 cells was collected and added to N2a cells. As shown in Figure 6A, LPS plus ATP-CM or Aβ 25−35 -CM promoted the apoptosis of N2a cells.…”

Tart Cherry Extracts Reduce Inflammatory and Oxidative Stress Signaling in Microglial Cells

“…Alternatively, microglial activation can be problematic, due to the release of potentially neurotoxic substances [31]. Furthermore, inflammation in the central nervous system has been linked to autoimmune diseases such as multiple sclerosis [32] and central nervous system degenerative diseases [33], as well as accelerating disease progression and worsening symptoms [3]. Microglia, when in a highly activated state—such as that caused by stressors like LPS—produce inflammatory molecules such as cytokines, superoxide, and nitric oxide, ultimately leading to a cascade of pro-inflammatory proteins and cell death [34].…”

Gestational Exposure to Particulate Matter 2.5 (PM2.5) Leads to Spatial Memory Dysfunction and Neurodevelopmental Impairment in Hippocampus of Mice Offspring

“…Neuronal apoptosis induced by over-activation of microglia during neuroinflammation has been reported conducive to the pathology of CNS degenerative diseases (Feng et al, 2016), thus we speculate exposure to PM 2.5 may also induce apoptosis as well as neuroinflammation and glial cell activation, and the expressions of apoptosis-related genes in hippocampus of mice offspring were investigated subsequently. Prenatal exposure to air pollution has been associated with ASD risk.…”