Dataset Information

Electroacupuncture at GV20‑GB7 regulates mitophagy to protect against neurological deficits following intracerebral hemorrhage via inhibition of apoptosis.

ABSTRACT: The acupuncture penetrating line of Baihui (GV20) to Qubin (GB7) spans the parietal, frontal and temporal lobes. The present study aimed to elucidate the mechanism by which electroacupuncture (EA) at GV20‑GB7 regulates mitophagy in intracerebral hemorrhage (ICH) and whether it serves a neuroprotective role. A whole blood‑induced ICH model was used. Mitophagy‑regulating proteins, including BCL/adenovirus E1B 19 kDa‑interacting protein 3 (BNIP3), PTEN‑induced putative kinase 1 (PINK1), Parkin and apoptosis‑associated proteins were detected by western blotting; autophagy following ICH was evaluated by immunofluorescent techniques; morphological characteristics of mitophagy were observed using transmission electron microscopy; and TUNEL assay was performed to determine the number of apoptotic cells. Immunohistochemistry was used to detect p53 expression. The protective role of EA (GV20‑GB7) via enhanced mitophagy and suppressed apoptosis in ICH was further confirmed by decreased modified neurological severity score. The results showed that EA (GV20‑GB7) treatment upregulated mitochondrial autophagy following ICH and inhibited apoptotic cell death. The mechanism underlying EA (GV20‑GB7) treatment may involve inhibition of p53, an overlapping protein of autophagy and apoptosis. EA (GV20‑GB7) treatment decreased neurobehavioral deficits following ICH but pretreatment with 3‑methyladenine counteracted the beneficial effects of EA (GV20‑GB7) treatment. In conclusion, EA (GV20‑GB7) improved recovery from ICH by regulating the balance between mitophagy and apoptosis.

SUBMITTER: Guan R

PROVIDER: S-EPMC8127033 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundThis study sought to explore the mechanism underlying the therapeutic effects of electroacupuncture (EA) on spatial memory deficits caused by surgery.MethodsHepatic apex resection was performed under propofol-based total intravenous anesthesia. Male Sprague-Dawley rats were subjected to EA treatment or EA + mitochondrial division inhibitor-1 (mdivi-1) treatment once a day for three consecutive days after surgery. The Morris water maze test was used to evaluate the spatial memory of the rats after surgery. Tissue from the hippocampus of each rat was frozen and used for transcriptomic and proteomic analyses to identify potential targets for EA treatment. Western blotting was used to confirm the protein expression levels. The levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) were detected using commercial kits. The rat mitochondria were then isolated, and the activity of mitochondrial complex V was assessed.ResultsEA attenuated surgery-induced spatial memory deficits on postoperative day 3, while these effects were reversed by treatment with the mdivi-1 (P<0.05). Ribonucleic acid (RNA)-sequencing revealed that EA upregulated multiple metabolic pathways and the phosphatidylinositol 3‑kinas/protein kinase B signaling pathway. The proteomic and western blotting results suggested that the EA treatment substantially downregulated coiled-coil-helix-coiled-coil-helix domain containing 3 (ChChd3) expression in the hippocampus. The EA treatment significantly increased the autophagy-related protein levels, including phosphatase and tensin homolog-induced kinase 1, Parkin, MAP1LC3 (LC3), and Beclin1, and inhibited the production of ROS and inflammatory cytokine interleukin-1β in the hippocampus (P<0.05).ConclusionsThese results suggest that EA ameliorates postoperative spatial memory deficits and protects hippocampus from oxidative stress and inflammation through enhanced autophagy in an animal model of perioperative neurocognitive disorders (PNDs).

Project description:Neuroinflammation contributes to secondary brain injury following intracerebral hemorrhage (ICH). Triggering receptor expressed on myeloid cells 2 (TREM2) confers strong neuroprotective effect by suppressing neuroinflammatory response in experimental ischemic stroke. This study aimed to clarify the neuroprotective role of TREM2 and potential underlying mechanism in a mouse model of ICH and in vitro. Adeno-associated virus (AAV) and green fluorescent protein-lentivirus (GFP-LV) strategies were employed to enhance TREM2 expression in the C57/BL6 mice and BV2 cells, respectively. The adult male C57/BL6 mice were subjected to ICH by administration of collagenase-IV in 1 month after the AAV particles injection. An in vitro ICH model was performed with oxygen hemoglobin in BV2 cells. Toll-like receptor 4 (TLR4) antagonist TAK242 was applied at 6 h following ICH. Neurological function, TREM2, pro-inflammatory cytokines, brain water content and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were evaluated at 24 h following ICH. TLR4, NF-κB and mitogen-activated protein kinases (MAPK) signaling pathways were also determined by Western blot analysis at the same time point. The levels of TREM2 were increased at 12 h, peaked at 24 h and recovered on 7d following ICH. TREM2 overexpression ameliorated ICH induced neurological dysfunction, inhibited neuroinflammation, and attenuated apoptosis and brain edema. Further mechanistic study revealed that TREM2 overexpression inhibited TLR4 activation and NF-κB and MAPK signaling pathways. ICH increased the percentage of TUNEL-positive cells, which was markedly decreased by TREM2 overexpression. A similar improvement was also observed by the administration of TAK242 following ICH. TREM2 improves neurological dysfunction and attenuates neuroinflammation and neuronal apoptosis in the acute phase of ICH, which is, at least in part, mediated by negatively regulating TLR4 signaling pathway. These findings highlight TREM2 as a potential target for early brain injury following ICH.

Dataset Information

Electroacupuncture at GV20‑GB7 regulates mitophagy to protect against neurological deficits following intracerebral hemorrhage via inhibition of apoptosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets