Maternal inflammation induces immune activation of fetal microglia and leads to disrupted microglia immune responses, behavior, and learning performance in adulthood

TREM2 inhibits inflammatory responses in mouse microglia by suppressing the PI3K/NF‐κB signaling

“…TREM2 activated PI3 K in macrophage (Peng et al, 2010;Zhu et al, 2014), whereas, the PI3K/AKT signaling can control a variety of cellular proliferation and survival processes as well as inflammatory responses. Previous studies have shown that PI3K/AKT signaling negatively regulates LPS-induced acute inflammatory responses in microglia (Dong et al, 2014;Cianciulli et al, 2016;Schaafsma et al, 2017). Therefore, to further confirm the inhibitory effects of TREM2 in microglia, we investigated the pro-inflammatory mediators release, Akt phosphorylation and NF-kB activation after treatment with PI3K inhibitor in LPS-stimulated BV2 cells.…”

“…After TREM2 binds with the ligands exposed in microglia, the immunoreceptor tyrosinebased activation motif-based transduction complex is phosphorylated, which in turn activates the downstream signaling and finally leads to cellular response (Luo et al, 2014;Jay et al, 2015;Wang et al, 2016;Choi et al, 2017). Previous studies have shown that PI3K/AKT signaling negatively regulates LPS-induced acute inflammatory responses in microglia (Dong et al, 2014;Cianciulli et al, 2016;Schaafsma et al, 2017). Previous studies have shown that PI3K/AKT signaling negatively regulates LPS-induced acute inflammatory responses in microglia (Dong et al, 2014;Cianciulli et al, 2016;Schaafsma et al, 2017).…”

Microglial memory of early life stress and inflammation: Susceptibility to neurodegeneration in adulthood

“…Early life exposure to lipopolysaccharides (LPS), a widely used model of inflammation caused by infection with gram-negative bacteria, results in differential location of activated microglia in the brain, with sustained alterations in hippocampal microglia that become hypersensitive to inflammatory markers. These changes endure throughout adulthood and have negative effects on memory and learning (Schaafsma, Basterra et al 2017).…”

Current Evidence on Cell Death in Preterm Brain Injury in Human and Preclinical Models

“…Direct inflammatory lesions are induced in most of the preclinical models by an acute or chronic exposure to either gram-negative bacteria lipopolysaccharide (LPS) endotoxin or more recently by injection of interleukin-1β that leads to a persistent inflammatory response, astrogliosis, and myelination deficits (Dean et al, 2015). It has been shown that exposure to inflammation during the perinatal period could alter transiently or permanently neurodevelopmental outcome (learning and motor difficulties and development of psychiatric disease such as schizophrenia or autism) (Fan et al, 2005b;Boksa, 2010;Rousset et al, 2013;Schaafsma et al, 2017;Straley et al, 2017;Zhang et al, 2018). Cell death has been mostly investigated in models of fetal infection in rat, sheep, and macaques in which apoptotic cell death (c-CASP3) was found to be scattered, located essentially in WM, and observed mainly after days following inflammatory insult ( Table 3).…”