ATF4/TRIB3 Pathway Regulating Hippocampal Neuronal Injury and Mitochondrial Unfolded Protein Response in Epilepsy

Yao MA; Guohui ZU; Jiarong LIU; Haifeng ZHANG; Lu LING

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Yao MA, Guohui ZU, Jiarong LIU, Haifeng ZHANG, Lu LING. ATF4/TRIB3 Pathway Regulating Hippocampal Neuronal Injury and Mitochondrial Unfolded Protein Response in Epilepsy[J]. Journal of Kunming Medical University.

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ATF4/TRIB3 Pathway Regulating Hippocampal Neuronal Injury and Mitochondrial Unfolded Protein Response in Epilepsy

1.
Department of Neurology，Hebei Third Veterans and Disabled Persons Hospital，Baoding Hebei 071000
2.
Department of Neurology，First Affiliated Hospital of Hebei Medical University，Shijiazhuang Hebei 050000，China

Received Date: 2025-04-24
Available Online: 2026-05-24

Abstract

Abstract

Objective This study aims to explore the interplay between autophagy and apoptosis in heart failure （HF） induced by pressure overload. Methods SD rats aged 6 weeks were used, and the EP model was established by pilocarpine induction. They were randomly divided into Sham group, EP model group and lv-ATF4 group （n = 10）. qRT-PCR was used to detect the expression levels of activating transcription factor 4 （ATF4） and tribble homologue 3 （TRIB3） in EP rats. Morris water maze and Racine score were used to evaluate the severity of epilepsy in rats. Nissl and HE staining were performed to observe the morphological structure of hippocampal tissue. TUNEL assay was used to detect the apoptosis of hippocampal neurons. Western blot was applied to detect the expression of mitochondrial unfolded protein response （mtUPR）-related proteins. The mitochondrial function indexes in hippocampal tissue were determined by assay kits. Results The expression of ATF4 and TRIB3 was decreased in the brain tissue of EP rats, and overexpression of ATF4 significantly promoted the expression of TRIB3.The Racine score and escape latency in the EP group were higher than those in the Sham group （P < 0.05）, while the number of crossings of the original platform was lower than that in the Sham group （P < 0.05）. The Racine score and escape latency in the lv-ATF4 group were lower than those in the EP group （P < 0.05）, and the number of crossings of the original platform was higher than that in the Sham group （P < 0.05）.In addition, overexpression of ATF4 reversed the pathological damage and hippocampal neuronal apoptosis in the hippocampal CA1 region of EP rats.The expression of mtUPR-related proteins and mitochondrial function indexes in the hippocampal tissue of the lv-ATF4 group were increased compared with the EP group （P < 0.05）. Conclusion Through in vivo and in vitro experiments, it was found that in the EP model established by pilocarpine, the ATF4/TRIB3 pathway was involved in the damage of hippocampal neurons and the protein response of mtUPR.
- ATF4/TRIB3,
- mitochondrial unfolded protein response,
- Epilepsy,
- Hippocampal Neuronal Injury

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References(26)

References

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