Honokiol protects brain against ischemia–reperfusion injury in rats through disrupting PSD95–nNOS interaction

Hu, Zhenyu; Bian, Xue-Bin; Liu, Xiaoyan; Zhu, Yuyan; Zhang, Xiaoyi; Chen, Shizhong; Wang, Kewei; Wang, Yinye

doi:10.1016/j.brainres.2012.11.004

Cited by 53 publications

(27 citation statements)

References 31 publications

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“…For example, it was reported that neuronal nitric-oxide synthase (nNOS)-PSD95 protein-protein interaction is important in maintaining hypersensitivity in acute and chronic pain and disruption of the nNOS-PSD95 interaction could inhibit acute thermal hyperalgesia and chronic mechanical allodynia (Florio et al, 2009). PSD95 was also implicated in the regulation of ischemic injury through nNOS-PSD95 (Hu et al, 2013) interaction and the glutamate receptor 6 (GluR6)-PSD95-calmodulin-dependent protein kinase II (CaMKII) signaling module (Xu et al, 2010). However, whether and how decreased PSD95 expression was involved in cognitive impairment remains elusive.…”

Section: Discussionmentioning

confidence: 99%

Decreased PSD95 expression in medial prefrontal cortex (mPFC) was associated with cognitive impairment induced by sevoflurane anesthesia

Ling

Ma²,

et al. 2015

J. Zhejiang Univ. Sci. B

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Abstract:Objective: Though sevoflurane has been widely used as an anesthetic in surgery, recent studies have shown that exposure to sevoflurane alone could lead to postoperative cognitive dysfunction (POCD), of which the mechanisms still remain largely unknown. The medial prefrontal cortex (mPFC) is known to be implicated in various cognitive impairments, including working memory and attentional processes. In the present study, we tried to identify dysregulated gene expression in mPFC and investigate the underlying mechanisms involved in POCD. Methods: Behavioral tests, including elevated plus-maze, O-maze, and Y-maze tests, were performed on Wistar rats exposed to sevoflurane. Whole-genome mRNA profiling of mPFC from Wistar rats after exposure to sevoflurane was carried out. Real-time polymerase chain reaction (PCR) was done to verify the differentially expressed genes. Results: Significant impairment of working memory of rats after exposure to sevoflurane was observed. A total of 119 of 7319 detected mRNAs showed significantly different expression between rats with and without sevoflurane exposure (fold change (FC)>2.0, P<0.05, and false discovery rate (FDR)<0.05), among which 74 mRNAs were down-regulated and 45 mRNAs were up-regulated. Postsynaptic density-95 (PSD95, also named DLG4) showed the most significantly decreased expression in mPFC and further investigation indicated that PSD95 expression level was correlated with spatial working memory performance. Conclusions: Our study revealed that PSD95 might be involved in the mechanism of POCD, which could provide clues for preventing POCD in clinical operations.

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Section: Discussionmentioning

confidence: 99%

Decreased PSD95 expression in medial prefrontal cortex (mPFC) was associated with cognitive impairment induced by sevoflurane anesthesia

Ling

Ma²,

et al. 2015

J. Zhejiang Univ. Sci. B

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“…Focal cerebral ischemia was induced by transient occlusion of the middle cerebral artery (MCAO) using the intraluminal filament technique as described previously [48]. Briefly, rats were anesthetized with chloral hydrate (350 mg/kg, i.p.…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective Effect of TAT-14-3-3ε Fusion Protein against Cerebral Ischemia/Reperfusion Injury in Rats

Zhu

Liu

et al. 2014

PLoS ONE

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Stroke is the major cause of death and disability worldwide, and the thrombolytic therapy currently available was unsatisfactory. 14-3-3ε is a well characterized member of 14-3-3 family, and has been reported to protect neurons against apoptosis in cerebral ischemia. However, it cannot transverse blood brain barrier (BBB) due to its large size. A protein transduction domain (PTD) of HIV TAT protein, is capable of delivering a large variety of proteins into the brain. In this study, we generated a fusion protein TAT-14-3-3ε, and evaluated its potential neuroprotective effect in rat focal ischemia/reperfusion (I/R) model. Western blot analysis validated the efficient transduction of TAT-14-3-3ε fusion protein into brain via a route of intravenous injection. TAT-14-3-3ε pre-treatment 2 h before ischemia significantly reduced cerebral infarction volume and improved neurologic score, while post-treatment 2 h after ischemia was less effective. Importantly, pre- or post-ischemic treatment with TAT-14-3-3ε significantly increased the number of surviving neurons as determined by Nissl staining, and attenuated I/R-induced neuronal apoptosis as showed by the decrease in apoptotic cell numbers and the inhibition of caspase-3 activity. Moreover, the introduction of 14-3-3ε into brain by TAT-mediated delivering reduced the formation of autophagosome, attenuated LC3B-II upregulation and reversed p62 downregulation induced by ischemic injury. Such inhibition of autophagy was reversed by treatment with an autophagy inducer rapamycin (RAP), which also attenuated the neuroprotective effect of TAT-14-3-3ε. Conversely, autophagy inhibitor 3-methyladenine (3-MA) inhibited I/R-induced the increase in autophagic activity, and attenuated I/R-induced brain infarct. These results suggest that TAT-14-3-3ε can be efficiently transduced into brain and exert significantly protective effect against brain ischemic injury through inhibiting neuronal apoptosis and autophagic activation.

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“…[7][8][9][10] It is worth mentioning that Tat-NR2B9c is safe and effective in treatment of patients with iatrogenic stroke after endovascular aneurysm repair. 11 In addition, disrupting nNOS-PSd-95 interaction via ZL006, 12 IC87201, 13 honokiol, 14 4-phenyl-1-(4-phenylbutyl)-piperidine, 15 and tramiprosate 16 can prevent excitotoxicity and does not influence nNOS catalytic activity.…”

Section: Glun2b/psd-95/nnos Complexmentioning

confidence: 99%

Therapeutic Targets for Cerebral Ischemia Based on the Signaling Pathways of the GluN2B C Terminus

Sun

Zhang

You

et al. 2015

Stroke

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Honokiol protects brain against ischemia–reperfusion injury in rats through disrupting PSD95–nNOS interaction

Cited by 53 publications

References 31 publications

Decreased PSD95 expression in medial prefrontal cortex (mPFC) was associated with cognitive impairment induced by sevoflurane anesthesia

Decreased PSD95 expression in medial prefrontal cortex (mPFC) was associated with cognitive impairment induced by sevoflurane anesthesia

Neuroprotective Effect of TAT-14-3-3ε Fusion Protein against Cerebral Ischemia/Reperfusion Injury in Rats

Therapeutic Targets for Cerebral Ischemia Based on the Signaling Pathways of the GluN2B C Terminus

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