The absorption of apolipoprotein E by damaged neurons facilitates neuronal repair

Abstract

Traumatic brain injury (TBI) is one of the common diseases diagnosed in departments of neurosurgery. Apolipoprotein E (apoE) can improve the prognosis of TBI. In this study, we aimed to explore the effect of apoE in mechanically damaging neurons as well as its underlying molecular mechanism. Western blot analysis and immunofluorescence assay was performed to detect the expressions of associated proteins. The expressions of apoE, p38, and phosphorylation of P38 were increased in mechanically injured neurons compared with those of the non‐injured ones. Neurons transfected into silencing apoE had no clear difference in the expression of apoE between injured and non‐injured neurons. However, in the injured neurons, silencing apoE could significantly decrease apoE and p‐P38 expressions. Oligodendrocytes were cultured in the medium collected from mechanically damaged si‐apoE neurons. Furthermore, we found that mechanically injured si‐apoE neurons could absorb the secreted apoE from the oligodendrocyte medium of the injured si‐apoE‐neuron, along with increasing of p‐P38 expression at 24 h. The p38 MAPK inhibitor BIRB 796 almost did not affect the apoE expression at 24 h, but significantly reduced the p‐P38 level at 24 and 72 h in injured si‐apoE neurons cultured with oligodendrocyte medium of the injured si‐apoE‐neurons. Moreover, our result showed that neuronal repair effects in normal neurobasal medium (lowest levels of apoE and p‐P38) and BIRB 796 medium (low level of p‐P38) were more slow than those in the oligodendrocyte medium of the injured si‐apoE‐neurons. To conclude, our data demonstrated that mechanical injury of neurons stimulated oligodendrocytes to secrete apoE. The injured neurons could absorb secreted apoE. The expression of apoE contributed to the activation of p38 MAPK, which facilitated neuron repair.

Sphingosine-1-phosphate, a novel TREM2 ligand, promotes microglial phagocytosis to protect against ischemic brain injury

“…APOE has been shown to regulate microglial phagocytosis via TREM2 35 , 46 . During ischemic stroke, APOE is not synthesized by neuron and its expression in astrocytes and microglia increases 30 .…”

The correlation between APOE expression and the clinical characteristics and prognosis of patients with endometrial cancer

“…[ 29 ] Researches on brain neurons have shown that APOE affects the growth and regeneration of axons in vitro through MAPK signaling pathways, [ 30 ] and injured neurons can absorb and secrete APOE to promote neuron repair by activating MAPK signaling pathways. [ 31 ] In addition, studies have shown that the metabolic regulation of APOE in human liver cells is affected by interfering MAPK/extracellular regulated protein kinases (ERK) signaling pathway, [ 32 ] and APOE stimulates the survival of neural stem cells through regulating MAPK/ERK signaling pathway. [ 33 ] Since APOE is related to the ERK signaling pathway, can APOE affect EC metastasis through the ERK signaling pathway?…”

Analysis of the lipid plasma spectrum in patients with long-term consequences after traumatic brain injury

“…Many foreign reports have shown that dyslipidemia often develops in patients with long-term consequences after TBI [1,5,6,13,14,16]. Changes in lipid spectrum may be explained by the fact that neurotrauma itself leads to a decreased rate of lipid decomposition due to reduced activity of lipoprotein lipase enzyme associated with decreasing rate of total cholesterol clearance [2, 14,15,20].…”

“…According to numerous literature data [1,2,5,6,10,11], neurotrauma itself may lead to the development of dyslipidemia due to the increased lipid degradation. Some authors showed that in children dyslipidemia was one of the main trigger factors that caused some metabolic syndromes [4].…”

“…Also, α-tocopherol, β-carotene, and ascorbic acid play a certain important role in antiatherogenic processes and dyslipidemia [12]. In vitro experiments have shown that lipid peroxidation did not begin until oxidative processes deplete stores of vitamin E and β-carotene [5,6].…”