Melatonin improves vascular cognitive impairment induced by ischemic stroke by remyelination via activation of ERK1/2 signaling and restoration of glutamatergic synapses in the gerbil hippocampus

Chen, Bai Hui; Park, Joon Ha; Lee, Yun Lyul; Kang, Il Jun; Kim, Dae Won; Hwang, In Koo; Lee, Choong‐Hyun; Yan, Bing Chun; Kim, Young‐Myeong; Lee, Tae-Kyeong; Lee, Jae Chul; Won, Moo‐Ho; Ahn, Ji Hyeon

doi:10.1016/j.biopha.2018.09.077

Cited by 37 publications

(44 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its pharmacological effects can be exerted in various nervous system diseases, such as repairing vascular cognitive impairment by activating ERK1/2 signaling pathway, and improving CIRI process by inhibiting endoplasmic reticulum stress and nerve cell apoptosis. 19 , 25 , 26 In this study, we found that MT played an anti-CIRI protective role in vivo and in vitro by inhibiting neuronal apoptosis, autophagy, inflammation and oxidative stress.…”

Section: Discussionmentioning

confidence: 62%

<p>Melatonin Plays a Protective Role by Regulating miR-26a-5p-NRSF and JAK2-STAT3 Pathway to Improve Autophagy, Inflammation and Oxidative Stress of Cerebral Ischemia-Reperfusion Injury</p>

Yang¹,

Zang²,

Cui³

et al. 2020

DDDT

View full text Add to dashboard Cite

Background Melatonin (MT) has potential protective effect on cerebral ischemia-reperfusion injury (CIRI), but its underlying regulatory mechanism has not been identified. Purpose This study aimed to explore the role of miR-26a-5p-neuron-restrictive silencing factor (NRSF/REST), Janus kinase-2 (JAK2)-signal transducer and activator of transcription-3 (STAT3) pathway in the protection mechanism of MT against CIRI in vivo and in vitro. Methods Sprague Dawley rats were induced with ischemia-reperfusion (IR) in vivo model; PC12 cells were induced with oxygen-glucose deprivation/reperfusion (OGD/R) in vitro model; and MT intervention was conducted before the model was established. The effect of MT on autophagy factors (LC3II/LC3I, P62), inflammatory factors (TNF-α, IL-6, IL-10) and oxidative stress indexes (MDA, GSHPx, SOD) was explored, and then the above three indexes were determined by real-time quantitative PCR, ELISA, and detection kit corresponding to oxidative stress indexes. The neuroprotective effect of MT pretreatment on brain IR injury was evaluated by neurological deficit scores and TUNEL method. The levels of miR-26a-5p and NRSF were detected by real-time quantitative PCR and Western blot, and the interaction between them was evaluated by dual luciferase report. The role of JAK2-STAT3 pathway in MT protection mechanism was verified by pathway blocker (AG490) and Western blot. Results MT pretreatment can significantly reduce neurological deficit score and neuronal apoptosis, inhibit CIRI autophagy, inflammation and oxidative stress in vivo and in vitro, reduce LC3II/LC3I, TNF-α, IL-6, MDA and increase P62, IL-10, GSHPx, SOD. Further analysis identifies that downregulating miR-26a-5p or upregulating NRSF can eliminate the protective effect of MT, and NRSF is the direct target of miR-26a-5p. The protective effect of MT can also be eliminated under AG490 intervention. Conclusion MT plays a protective role by regulating miR-26a-5p-NRSF and JAK2-STAT3 pathway to improve CIRI autophagy, inflammation and oxidative stress.

show abstract

Section: Discussionmentioning

confidence: 62%

<p>Melatonin Plays a Protective Role by Regulating miR-26a-5p-NRSF and JAK2-STAT3 Pathway to Improve Autophagy, Inflammation and Oxidative Stress of Cerebral Ischemia-Reperfusion Injury</p>

Yang¹,

Zang²,

Cui³

et al. 2020

DDDT

View full text Add to dashboard Cite

show abstract

“…The hippocampus is one of substructures vulnerable to ischemic insults, and the hippocampal injury is prone to declines in memory and learning [ 22 , 23 ]. In particular, these declines are easily shown in a gerbil model of TFI for 5 min, because this model gives rise to death of pyramidal neurons located in the SP of the hippocampal CA1 region about 4–5 days later [ 6 , 24 , 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Experimental Pretreatment with Chlorogenic Acid Prevents Transient Ischemia-Induced Cognitive Decline and Neuronal Damage in the Hippocampus through Anti-Oxidative and Anti-Inflammatory Effects

et al. 2020

Self Cite

View full text Add to dashboard Cite

Chlorogenic acid (CGA), an ester of caffeic acid and quinic acid, is among the phenolic acid compounds which can be naturally found in green coffee extract and tea. CGA has been studied since it displays significant pharmacological properties. The aim of this study was to investigate the effects of CGA on cognitive function and neuroprotection including its mechanisms in the hippocampus following transient forebrain ischemia in gerbils. Memory and learning following the ischemia was investigated by eight-arm radial maze and passive avoidance tests. Neuroprotection was examined by immunohistochemistry for neuronal nuclei-specific protein and Fluoro-Jade B histofluorescence staining. For mechanisms of the neuroprotection, alterations in copper, zinc-superoxide dismutase (SOD1), SOD2 as antioxidant enzymes, dihydroethidium and 4-hydroxy-2-nonenal as indicators for oxidative stress, and anti-inflammatory cytokines (interleukin (IL)-4 and IL-13) and pro-inflammatory cytokines (tumor necrosis factor α (TNF-α) and IL-2) were examined by Western blotting and/or immunohistochemistry. As a result, pretreatment with 30 mg/kg CGA attenuated cognitive impairment and displayed a neuroprotective effect against transient forebrain ischemia (TFI). In Western blotting, the expression levels of SOD2 and IL-4 were increased due to pretreatment with CGA and, furthermore, 4-HNE production and IL-4 expressions were inhibited by CGA pretreatment. Additionally, pretreated CGA enhanced antioxidant enzymes and anti-inflammatory cytokines and, in contrast, attenuated oxidative stress and pro-inflammatory cytokine expression. Based on these results, we suggest that CGA can be a useful neuroprotective material against ischemia-reperfusion injury due to its antioxidant and anti-inflammatory efficacies.

show abstract

“…The genes identified via GO and KEGG analyses in the present study may indicate novel molecules or pathways underlying PnS treatment of ischemic stroke. Glutamatergic synapses and calcium signaling are known to play important roles in cerebral ischemia, contributing to neuronal death after a stroke (29,30). under ischemic stroke conditions, neuronal calcium signaling participates in endothelial restoration Figure 6.…”

Section: Discussionmentioning

confidence: 99%

Using mRNA deep sequencing to analyze differentially expressed genes during Panax notoginseng saponin treatment of ischemic stroke

et al. 2020

View full text Add to dashboard Cite

Treatment with Panax notoginseng saponin (PnS) can prevent neurological damage in middle cerebral artery occlusion model rats to promote recovery after a stroke. However, the exact molecular mechanisms are unknown and require further study. in the present study, mrna sequencing was employed to investigate differential gene expression between model and sham groups, and between model and PnS-treated groups. enrichment of gene data was performed using Gene ontology analysis and the Kyoto encyclopedia of Genes and Genomes database. Hub genes were identified and networks were constructed using Cytoscape that were further verified by reverse transcription-quantitative Pcr. a total of 1,104 genes of interest were found, which included 690 upregulated and 414 downregulated genes that were identified when the model was compared with the sham group. additionally, 817 genes of interest, which included 390 upregulated and 427 downregulated genes, were identified when the PNS-treated group was compared with the model group. There were 303 overlapping genes of interest between the analysis of model to sham groups, and the analysis of model to PnS-treated groups. The top 10 genes from the 303 aberrantly expressed genes of interest included ubiquitin conjugating enzyme e2 variant 2, small ubiquitin-related modifier 1, small RNA binding exonuclease protection factor la, Finkel-Biskis-reilly murine sarcoma virus (FBr-MuSV) ubiquitously expressed, centrosomal protein 290 kda, dna-directed rna polymerase ii subunit K, cullin-4B, matrin-3 and vascular endothelial growth factor receptor 2. in conclusion, these genes may be important in the underlying mechanism of PnS treatment in ischemic stroke. additionally, the present data provided novel insight into the pathogenesis of ischemic stroke.

show abstract

Melatonin improves vascular cognitive impairment induced by ischemic stroke by remyelination via activation of ERK1/2 signaling and restoration of glutamatergic synapses in the gerbil hippocampus

Cited by 37 publications

References 53 publications

<p>Melatonin Plays a Protective Role by Regulating miR-26a-5p-NRSF and JAK2-STAT3 Pathway to Improve Autophagy, Inflammation and Oxidative Stress of Cerebral Ischemia-Reperfusion Injury</p>

<p>Melatonin Plays a Protective Role by Regulating miR-26a-5p-NRSF and JAK2-STAT3 Pathway to Improve Autophagy, Inflammation and Oxidative Stress of Cerebral Ischemia-Reperfusion Injury</p>

Experimental Pretreatment with Chlorogenic Acid Prevents Transient Ischemia-Induced Cognitive Decline and Neuronal Damage in the Hippocampus through Anti-Oxidative and Anti-Inflammatory Effects

Using mRNA deep sequencing to analyze differentially expressed genes during Panax notoginseng saponin treatment of ischemic stroke

Contact Info

Product

Resources

About