Homer 1a overexpression alleviates nerve injury in mice with traumatic brain injury by regulating autophagy mediated by PI3K/AKT/mTOR pathway.
- Author:
Yuan WANG
1
;
Mengyang WANG
1
;
Xiumin ZHANG
1
;
Ming LUO
2
,
3
Author Information
1. Department of Neurosurgery, Wuhan NO.1 Hospital, Wuhan 432000, China.
2. Department of Neurosurgery, Wuhan NO.1 Hospital, Wuhan 432000, China. *Corresponding author, E-mail: luoming202111@
3. com.
- Publication Type:Journal Article
- MeSH:
Animals;
TOR Serine-Threonine Kinases/genetics*;
Autophagy;
Brain Injuries, Traumatic/pathology*;
Male;
Proto-Oncogene Proteins c-akt/genetics*;
Phosphatidylinositol 3-Kinases/genetics*;
Homer Scaffolding Proteins/metabolism*;
Mice, Inbred C57BL;
Signal Transduction;
Mice
- From:
Chinese Journal of Cellular and Molecular Immunology
2025;41(1):31-37
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects and molecular mechanism of Homer protein homolog 1a (Homer 1a) overexpression on nerve injury in mice with traumatic brain injury (TBI). Methods Sixty male C57BL/6 mice were randomly divided into five groups: sham group, TBI group, empty lentivirus (Lv-NC) group, Homer 1a overexpression lentivirus (Lv-Homer 1a) group and Lv-Homer 1a + 740 Y-P group, with 12 mice in each group. The lentivirus was orthotopic injected into the cerebral cortex of mice 5 d before modeling, while 740 Y-P was injected intraperitoneally 1 d before modeling. The TBI model was established using the free-fall impact method, and the modified neurological severity scores (mNSS) of the mice was assessed 72 h post-surgery. The water content of brain tissue was quantified, and the histopathological damage and neuronal loss in brain tissue were assessed using HE staining and Nissl staining respectively. The formation of autophagosomes in brain tissue was observed by transmission electron microscopy. The protein expression levels of Homer 1a, microtubule-associated protein 1 light chain 3B (LC3B), Beclin 1, phosphatidylinositol 3-kinase (PI3K), phosphorylation PI3K(p-PI3K), protein kinase B (AKT), p-AKT, mammalian target of rapamycin (mTOR), and p-mTOR in brain tissue were detected by Western blot analysis. Results Compared to the sham group, the mice in the TBI group exhibited a significant increase in mNSS and cerebral water content. Moreover, severe brain tissue pathological damage was observed, accompanied by a substantial loss of neurons and an increase in autophagosome formation. The protein expressions of Homer 1a and Beclin 1, as well as the protein ratio of LC3B-II/LC3B-I, in brain tissues were significantly elevated, while the protein ratios of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR were significantly reduced. Compared to the TBI group, the Lv-Homer 1a group exhibited reduced mNSS and brain water content. Additionally, there was an improvement in pathological brain tissue damage and neuron loss. Furthermore, there was an increase in autophagosome formation and expression of autophagy-related proteins, while the protein ratios of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR were decreased. Compared to the Lv-Homer 1a group, the nerve injury in the Lv-Homer 1a+740 Y-P group was exacerbated, accompanied by a reduction in autophagosome formation and expression of autophagy-related proteins, while the PI3K/AKT/mTOR signaling pathway was activated. Conclusion Overexpression of Homer 1a effectively mitigates neurological damage in TBI mice, potentially through modulation of autophagy mediated by the PI3K/AKT/mTOR signaling pathway.
