RETRACTED ARTICLE: Role of p75 neurotrophin receptor in neuronal autophagy in intracerebral hemorrhage in rats through the mTOR signaling pathway

Abstract

Rupture of weakened blood vessels could lead to severe intracerebral hemorrhage (ICH) and brain injuries. This study was designed to explore the roles of p75 neurotrophin receptor (p75 NTR) in neuronal autophagy in ICH rats. An ICH rat model was established, and then gain and loss of functions of p75 NTR in rat tissues were performed. Then, the pathologic morphology, water content, and inflammation in brain tissues were assessed. Western blot analysis was applied to detect the levels of inflammatory proteins, apoptosis-and autophagy-related proteins, and the mammalian target of rapamycin (mTOR) pathwayrelated proteins. Neuronal autophagy was further measured with mTOR activated. In vitro experiments were also performed on brain microvascular endothelial cells (BMECs) and astrocytes. Consequently, we found p75 NTR knockdown improved the pathologic morphology with reduced neuron damage, water content, permeability of blood-brain barrier and inflammation in ICH rat brain tissues. Besides, Knockdown of p75 NTR decreased neuronal apoptosis and inactivated mTOR signaling pathway, but it elevated the levels of autophagy-related proteins. In vivo results were reproduced in in vitro experiments. This study demonstrated that knockdown of p75 NTR could promote neuronal autophagy and reduce neuronal apoptosis via inactivating the mTOR pathway. We hope these findings could provide new therapeutic options for ICH treatment.

An Shen Ding Zhi Ling Ameliorates the Symptoms of Attention Deficit Hyperactivity Disorder via Modulating Brain-Derived Neurotrophic Factor-Related Signaling Pathways

“…We suspected that this might also affect the release of DA from synaptic vesicles. The P75 neurotrophic factor receptor (P75NTR) is a transmembrane glycoprotein and a low-affinity receptor for BDNF, binding to neurotrophic factors in regulating various functions [ 61 ]. The death domain of P75NTR interacts with a large number of intracellular molecules and regulates different signaling cascades, including NF- κ B and JNK/caspase pathways in different cellular contexts [ 62 , 63 ].…”

“…We suspected that this might also affect the release of DA from synaptic vesicles. e P75 neurotrophic factor receptor (P75NTR) is a transmembrane glycoprotein and a low-affinity receptor for BDNF, binding to neurotrophic factors in regulating various functions [61].…”

Autophagy regulates inflammation in intracerebral hemorrhage: Enemy or friend?

“…The primary possible reason is that autophagy flux was damaged 72 h after ICH and restored to integrity after 7 days ( Duan et al, 2017 ). Furthermore, Wang et al found that the knockdown of the p75 neurotrophin receptor (p75NTR) could promote neuronal autophagy by inactivating the mTOR pathway, presenting protective roles in a rat model of ICH ( Wang L. et al, 2020 ).…”

The use of multiple datasets to identify autophagy-related molecular mechanisms in intracerebral hemorrhage

“…When iron overload and abnormal thrombin expression occur in brain tissue, autophagy is activated and involved in the brain protection process to reduce injury, remove harmful substances and maintain intracellular environmental homeostasis. The protective role of autophagy in ICH has been demonstrated ( Wang et al, 2020 ; Li et al, 2021 ). However, the overactivation of autophagy, which activates microglia to produce proinflammatory factors and damages neurons, leads to the aggravation of secondary injury after ICH ( Shi et al, 2018 ; Zhang et al, 2021 ).…”