Tramiprosate protects neurons against ischemic stroke by disrupting the interaction between PSD95 and nNOS

Wu, Shuangchan; Yue, Yuan; Tian, Hui; Li, Tao; Wang, Yuting; Xiang, Jin; Wang, Shi; Ding, Hong

doi:10.1016/j.neuropharm.2014.04.010

Cited by 38 publications

(37 citation statements)

References 54 publications

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“…In complete nNOS knockout mice, there is an attenuation of contextual fear conditioning and spatial memory formation similar to what is observed in Tat transgenic mice (Kirchner et al 2004; Weitzdoerfer et al 2004; Kelley et al 2009; Fitting et al 2013). While nNOS is important for normal hippocampal function (Kirchner et al 2004; Zanelli et al 2009), research indicates that nNOS-induced neuronal damage occurs in pathological states (Cui et al 2007; Eugenin et al 2007; Steinert et al 2010; Wang et al 2010; Drury et al 2014; Hsu et al 2014; Wu et al 2014). The role of nNOS in excitotoxicity, including HIV-1 Tat excitotoxicity, is reportedly linked to its activation of PSD-95 and NMDA receptor complexes (Christopherson et al 1999; Eugenin et al 2007; Fan et al 2010; King et al 2010; Steinert et al 2010).…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Tat causes cognitive deficits and selective loss of parvalbumin, somatostatin, and neuronal nitric oxide synthase expressing hippocampal CA1 interneuron subpopulations

et al. 2016

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Memory deficits are characteristic of HIV-associated neurocognitive disorders (HAND) and co-occur with hippocampal pathology. The HIV-1 transactivator of transcription (Tat), a regulatory protein, plays a significant role in these events, but the cellular mechanisms involved are poorly understood. Within the hippocampus, diverse populations of interneurons form complex networks; even subtle disruptions can drastically alter synaptic output, resulting in behavioral dysfunction. We hypothesized that HIV-1 Tat would impair cognitive behavior and injure specific hippocampal interneuron subtypes. Male transgenic mice that inducibly expressed HIV-1 Tat (or non-expressing controls) were assessed for cognitive behavior or had hippocampal CA1 subregions evaluated via interneuron subpopulation markers. Tat exposure decreased spatial memory in a Barnes maze and mnemonic performance in a novel object recognition test. Tat reduced the percentage of neurons expressing neuronal nitric oxide synthase (nNOS) without neuropeptide Y immunoreactivity in the stratum pyramidale and the stratum radiatum, parvalbumin in the stratum pyramidale, and somatostatin in the stratum oriens, which are consistent with reductions in interneuron-specific interneuron type 3 (IS3), bistratified, and oriens-lacunosum-moleculare interneurons, respectively. The findings reveal that an interconnected ensemble of CA1 nNOS-expressing interneurons, the IS3 cells, as well as subpopulations of parvalbumin- and somatostatin-expressing interneurons are preferentially vulnerable to HIV-1 Tat. Importantly, the susceptible interneurons form a microcircuit thought to be involved in feedback inhibition of CA1 pyramidal cells and gating of CA1 pyramidal cell inputs. The identification of vulnerable CA1 hippocampal interneurons may provide novel insight into the basic mechanisms underlying key functional and neurobehavioral deficits associated with HAND.

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Section: Discussionmentioning

confidence: 99%

HIV-1 Tat causes cognitive deficits and selective loss of parvalbumin, somatostatin, and neuronal nitric oxide synthase expressing hippocampal CA1 interneuron subpopulations

et al. 2016

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“…LDH activity was detected using a LDH activity assay kit according to the manufacturer's instructions [24]. Absorbance values were measured at 490 nm with a reference wavelength of 655 nm, using a 96-well microplate reader (Tecan Systems Inc., Oberdiessbach, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

Novel Therapeutic Effects of Leonurine On Ischemic Stroke: New Mechanisms of BBB Integrity

Zhang

Wang

Sun

et al. 2017

Oxidative Medicine and Cellular Longevity

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Stroke is a leading cause of morbidity and mortality globally. Leonurine (also named SCM-198), a compound extracted from Herba leonuri, was effective on the prevention of various cardiovascular and brain diseases. The purpose of this study was to explore the possible therapeutic potential of SCM-198 against ischemia reperfusion injury and underlying mechanisms. In the in vivo transient middle cerebral artery occlusion (tMCAO) rat model, we found that treatment with SCM-198 could decrease infarct volume and improve neurological deficit by protecting against blood-brain barrier (BBB) breakdown. In the in vitro model of cell oxygen-glucose deprivation and reoxygenation (OGD/R), consistent results were obtained with decreased reactive oxygen species (ROS) production and maintained the BBB integrity. Further study demonstrated that SCM-198 increased the expression of histone deacetylase- (HDAC-) 4 which could inhibit NADPH oxidase- (NOX-) 4 and matrix metalloproteinase- (MMP-) 9 expression, resulting in the elevation of tight junction proteins, including claudin-5, occludin, and zonula occluden- (ZO-) 1. These results indicated SCM-198 protected BBB integrity by regulating the HDAC4/NOX4/MMP-9 tight junction pathway. Our findings provided novel insights into the protective effects and mechanisms of SCM-198 on ischemic stroke, indicating SCM-198 as a new class of potential drug against acute onset of ischemic stroke.

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“…32 Protein lysates from both rats and Caco-2 cells were separated by 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). 32 Protein lysates from both rats and Caco-2 cells were separated by 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).…”

Section: Western Blottingmentioning

confidence: 99%

Wild jujube polysaccharides protect against experimental inflammatory bowel disease by enabling enhanced intestinal barrier function

Yue

et al. 2015

Food Funct.

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Dietary polysaccharides provide various beneficial effects for our health. We investigated the protective effects of wild jujube (Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou) sarcocarp polysaccharides (WJPs) against experimental inflammatory bowel disease (IBD) by enabling enhanced intestinal barrier function. Colitis was induced in rats by the intrarectal administration of TNBS. We found that WJPs markedly ameliorated the colitis severity, including less weight loss, decreased disease activity index scores, and improved mucosal damage in colitis rats. Moreover, WJPs suppressed the inflammatory response via attenuation of TNF-α, IL-1β, IL-6 and MPO activity in colitis rats. And then, to determine the effect of WJPs on the intestinal barrier, we measured the effect of WJPs on the transepithelial electrical resistance (TER) and FITC-conjugated dextran permeability in Caco-2 cell stimulation with TNF-α. We further demonstrated that the alleviation of WJPs to colon injury was associated with barrier function by assembly of tight junction proteins. Moreover, the effect of WJPs on TER was eliminated by the specific inhibitor of AMPK. AMPK activity was also up-regulated by WJPs in Caco-2 cell stimulation with TNF-α and in colitis rats. This study demonstrates that WJPs protect against IBD by enabling enhanced intestinal barrier function involving the activation of AMPK.

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Tramiprosate protects neurons against ischemic stroke by disrupting the interaction between PSD95 and nNOS

Cited by 38 publications

References 54 publications

HIV-1 Tat causes cognitive deficits and selective loss of parvalbumin, somatostatin, and neuronal nitric oxide synthase expressing hippocampal CA1 interneuron subpopulations

HIV-1 Tat causes cognitive deficits and selective loss of parvalbumin, somatostatin, and neuronal nitric oxide synthase expressing hippocampal CA1 interneuron subpopulations

Novel Therapeutic Effects of Leonurine On Ischemic Stroke: New Mechanisms of BBB Integrity

Wild jujube polysaccharides protect against experimental inflammatory bowel disease by enabling enhanced intestinal barrier function

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