Action of Akt Pathway on La-Induced Hippocampal Neuron Apoptosis of Rats in the Growth Stage

Qiangji Decoction (QJD), a classic formula, has been widely used to treat brain aging–related neurodegenerative diseases. However, the mechanisms underlying QJD’s improvement in cognitive impairment of neurodegenerative diseases remain unclear. In this study, we employed D-galactose to establish the model of brain aging by long-term D-galactose subcutaneous injection. Next, we investigated QJD’s effect on cognitive function of the model of brain aging and the mechanisms that QJD suppressing neuroinflammation as well as improving neurodegenerative changes and hippocampal neuron apoptosis. The mice of brain aging were treated with three different dosages of QJD (12.48, 24.96, and 49.92 g/kg/d, respectively) for 4 weeks. Morris water maze was used to determine the learning and memory ability of the mice. HE staining and FJB staining were used to detect the neurodegenerative changes. Nissl staining and TUNEL staining were employed to detect the hippocampal neuron apoptosis. The contents of TNF-α, IL-1β, and IL-6 in the hippocampus were detected by using ELISA. Meanwhile, we employed immunofluorescence staining to examine the levels of GFAP and IBA1 in the hippocampus. Besides, the protein expression levels of Bcl-2, Bax, caspase-3, cleaved caspase-3, AMPKα, p-AMPKα-Thr172, SIRT1, IκBα, NF-κB p65, p-IκBα-Ser32, and p-NF-κB p65-Ser536 in the hippocampus of different groups were detected by Western blot (WB). Our findings showed that the QJD-treated groups, especially the M-QJD group, mitigated learning and memory impairments of the model of brain aging as well as the improvement of neurodegenerative changes and hippocampal neuron apoptosis. Moreover, the M-QJD markedly attenuated the neuroinflammation by regulating the AMPK/SIRT1/NF-κB signaling pathway. Taken together, QJD alleviated neurodegenerative changes and hippocampal neuron apoptosis in the model of brain aging via regulating the AMPK/SIRT1/NF-κB signaling pathway.

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Endogenous sulfur dioxide regulates hippocampal neuron apoptosis in developing epileptic rats and is associated with the PERK signaling pathway

Neuroscience Letters ◽

10.1016/j.neulet.2017.11.036 ◽

2018 ◽

Vol 665 ◽

pp. 22-28 ◽

Cited By ~ 3

Author(s):

Manman Niu ◽

Ying Han ◽

Qinrui Li ◽

Jing Zhang

Keyword(s):

Sulfur Dioxide ◽

Signaling Pathway ◽

Hippocampal Neuron ◽

Neuron Apoptosis

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MicroRNA-383 upregulation protects against propofol-induced hippocampal neuron apoptosis and cognitive impairment

Experimental and Therapeutic Medicine ◽

10.3892/etm.2018.5838 ◽

2018 ◽

Cited By ~ 3

Author(s):

Xinlei Wang ◽

Guoyou Ding ◽

Wei Lai ◽

Shiwen Liu ◽

Jun Shuai

Keyword(s):

Cognitive Impairment ◽

Hippocampal Neuron ◽

Neuron Apoptosis

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Molecular Mechanism of ATF6α/S1P/S2P Signaling Pathway in Hippocampal Neuron Apoptosis in SPS Rats

10.21203/rs.3.rs-170376/v1 ◽

2021 ◽

Author(s):

liang han ◽

Yan hao Xu ◽

Yu xiu Shi

Keyword(s):

Mrna Expression ◽

Hippocampal Neurons ◽

Hippocampal Neuron ◽

Control Group ◽

Tunel Staining ◽

Apoptosis Rate ◽

Memory Disorder ◽

Caspase 12 ◽

Induced Apoptosis ◽

Neuron Apoptosis

Abstract Apoptosis of hippocampal neurons is one of the mechanisms of hippocampal atrophy in posttraumatic stress disorder (PTSD), and it is also one of the important reasons of memory disorder in PTSD patients. The endoplasmic reticulum stress (ERS) mediated by activated transcription factor 6α(ATF6α)/site 1 protease (S1P)/S2P is involved in cell apoptosis, but it is not clear whether it is involved in hippocampal neuron apoptosis caused by PTSD. The PTSD rat model was constructed by the single-prolonged stress (SPS) method. The experiment was divided into two parts: (1) Control group, SPS 1d group, SPS 7d group, SPS 14d group. (2) Control group, SPS 7d group, SPS 7d+AEBSF group, control+AEBSF group. 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) is an ATF6α pathway inhibitor. The expression of ATF6α, glucose regulated protein (GRP78), S1P, S2, C/EBP homologous protein (CHOP), caspase-12 protein and mRNA in the hippocampus of PTSD rats were detected by immunohistochemistry, Western blotting and qRT-PCR. The apoptosis of hippocampal neurons was detected by TUNEL staining. In experiment 1, the protein and mRNA expression of ATF6α, GRP78 increased gradually in SPS 1d group and SPS 7d group, but decreased in SPS 14d group(P<0.01). In experiment 2, compared with the control group, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, caspase-12 and apoptosis rate were significantly increased in SPS 7d group(P<0.01). However, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, caspase-12 and apoptosis rate were significantly decreased after AEBSF pretreatment(P<0.01). SPS induces apoptosis of hippocampal neurons by activating ERS mediated by ATF6α, suggesting that ERS-induced apoptosis is involved in the occurrence of PTSD.

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MiR-34a Inhibits Spinal Cord Injury and Blocks Spinal Cord Neuron Apoptosis by Activating Phatidylinositol 3-kinase (PI3K)/AKT Pathway Through Targeting CD47

Current Neurovascular Research ◽

10.2174/1567202616666190906102343 ◽

2019 ◽

Vol 16 (4) ◽

pp. 373-381 ◽

Cited By ~ 1

Author(s):

Liao Qi ◽

Ming Jiang-Hua ◽

Hu Ge-Liang ◽

Chen Qing ◽

Li Ya-Ming

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Rating Scale ◽

Akt Pathway ◽

Spinal Neuron ◽

Tunel Staining ◽

Cord Injury ◽

Weight Drop ◽

Related Proteins ◽

Neuron Apoptosis

Objective: Dysregulation of miR-34a has been reported for its implication in neuronal development. This study aims to explore the effect and possible mechanism of miR-34a on neuron apoptosis induced by Spinal Cord Injury (SCI). Materials and Methods: SCI model was established using Allen's weight-drop method and rats in the sham group were performed with laminectomy without weight-drop injury. Basso Bcattie Bresnahan (BBB) rating scale was applied to evaluate the locomotor function of rats. Pathological changes of spinal cord tissues in SCI rats were observed after hematoxylin and eosin (HE) staining. Rats were separately injected with miR-34a agomir, miR-34a agomir NC, si-CD47 and si- CD47 NC before their spinal cord tissues were collected for terminal-deoxynucleoitidyl Transferase Mediated nick end labeling (TUNEL) staining. Expressions of miR-34a, si-CD47, apoptosis related proteins and AKT pathway related proteins were measured by quantitative reverse transcription- polymerase chain reaction (qRT-PCR) and western blot. Results: SCI rat models were successfully established evidenced by decreased BBB scores and HE staining. Injection of miR-34a agomir and/or si-CD47 could suppress neuron cell apoptosis, with deceased apoptotic index (AI) and pro-apoptotic protein (cleaved caspase-3 and Bax) levels, and increased expressions of anti-apoptotic proteins (Bcl-2 and Mcl-1). Phosphorylated levels of phatidylinositol 3-kinase (PI3K) and AKT were further increased in rats injected with miR-34a agomir and si-CD47, compared with miR-34a agomir or si-CD47 injection alone. Conclusion: MiR-34a can downregulate CD47 expression to activate PI3K/AKT signal pathway, and thus inhibit SCI induced spinal neuron apoptosis.

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