Expression of complement regulators and receptors on human NT2-N neurons—Effect of hypoxia and reoxygenation

Pedersen, Elisabeth; Frøyland, Elisabeth; Kvissel, Anne-Katrine; Pharo, Anne; Skålhegg, Bjørn Steen; Rootwelt, Terje; Mollnes, Tom Eirik

doi:10.1016/j.molimm.2006.10.022

Cited by 28 publications

(29 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…57 The protein has complement-inhibitory properties, but its capability to mediate complement-mediated damage to neurons is also recognized. 58, 59, 60, 61 The CAT gene encodes catalase, a key antioxidant enzyme that serves as a defense against oxidative stress. Chronic unpredictable stress decreases CAT expression in the mouse cerebral cortex and hippocampus; 62 these effects may be mirrored by the decreased expression of this gene in the blood of both the chronic stress model and subjects with MDD.…”

Section: Discussionmentioning

confidence: 99%

Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression

et al. 2012

View full text Add to dashboard Cite

Early-onset major depressive disorder (MDD) is a serious and prevalent psychiatric illness in adolescents and young adults. Current treatments are not optimally effective. Biological markers of early-onset MDD could increase diagnostic specificity, but no such biomarker exists. Our innovative approach to biomarker discovery for early-onset MDD combined results from genome-wide transcriptomic profiles in the blood of two animal models of depression, representing the genetic and the environmental, stress-related, etiology of MDD. We carried out unbiased analyses of this combined set of 26 candidate blood transcriptomic markers in a sample of 15–19-year-old subjects with MDD (N=14) and subjects with no disorder (ND, N=14). A panel of 11 blood markers differentiated participants with early-onset MDD from the ND group. Additionally, a separate but partially overlapping panel of 18 transcripts distinguished subjects with MDD with or without comorbid anxiety. Four transcripts, discovered from the chronic stress animal model, correlated with maltreatment scores in youths. These pilot data suggest that our approach can lead to clinically valid diagnostic panels of blood transcripts for early-onset MDD, which could reduce diagnostic heterogeneity in this population and has the potential to advance individualized treatment strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Several studies have demonstrated the essential role of complement activation in brain damage following cerebral ischemia. Such evidence includes (i) an increased expression of complement proteins and complement receptors after permanent middle cerebral artery occlusion (MCAO) [8-11] (ii) different pathological events in complement-deficient/-sufficient animals after the onset of cerebral ischemia compared to wild-type littermates: complement deficient animals are at least partially protected after transient MCAO [12-15]. (iii) In rodent experimental models, complement depletion induced using the cobra venom factor (CVF) [16,17], as well as complement inhibition by a plasma-derived C1-inhibitor [18,19], a recombinant C1 inhibitor [20], CR2-Crry [13] and intravenous immunoglobulin administration [14] were proven to exert beneficial, neuroprotective effects, indicating the protective role of complement antagonism and inhibition.…”

Section: Introductionmentioning

confidence: 99%

Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke

Füst

Munthe-Fog

Illés

et al. 2011

Journal of Neuroinflammation

View full text Add to dashboard Cite

BackgroundA number of data indicate that the lectin pathway of complement activation contributes to the pathophysiology of ischemic stroke. The lectin pathway may be triggered by the binding of mannose-binding lectin (MBL), ficolin-2 or ficolin-3 to different ligands. Although several papers demonstrated the significance of MBL in ischemic stroke, the role of ficolins has not been examined.MethodsSera were obtained within 12 hours after the onset of ischemic stroke (admission samples) and 3-4 days later (follow-up samples) from 65 patients. The control group comprised 100 healthy individuals and 135 patients with significant carotid stenosis (patient controls). The concentrations of ficolin-2 and ficolin-3, initiator molecules of the lectin complement pathway, were measured by ELISA methods. Concentration of C-reactive protein (CRP) was also determined by a particle-enhanced immunturbidimetric assay.ResultsConcentrations of both ficolin-2 and ficolin-3 were significantly (p < 0.001) decreased in both the admission and in the follow-up samples of patients with definite ischemic stroke as compared to healthy subjects. Concentrations of ficolin-2 and ficolin-3 were even higher in patient controls than in healthy subjects, indicating that the decreased levels in sera during the acute phase of stroke are related to the acute ischemic event. Ficolin-3 levels in the follow-up samples inversely correlated with the severity of stroke indicated by NIH scale on admission. In follow-up samples an inverse correlation was observed between ficolin-3 levels and concentration of S100β, an indicator of the size of cerebral infarct. Patients with low ficolin-3 levels and high CRP levels in the follow up samples had a significantly worse outcome (adjusted ORs 5.6 and 3.9, respectively) as measured by the modified Rankin scale compared to patients with higher ficolin-3 and lower CRP concentrations. High CRP concentrations were similarly predictive for worse outcome, and the effects of low ficolin-3 and high CRP were independent.ConclusionsOur findings indicate that ficolin-mediated lectin pathways of complement activation contribute to the pathogenesis of ischemic stroke and may be additive to complement-independent inflammatory processes.

show abstract

“…Human NT2-N neurons constitutively express DAF which is down-regulated after severe hypoxia and subsequent reoxygenation with human serum [14]. It has been previously shown that increased expression of DAF plays an important role in the reduction of cerebral damage by steroids after Traumatic Brain Injury [15].…”

Section: Introductionmentioning

confidence: 99%

Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury

Wang

Lucca

et al. 2010

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundActivated complement system is known to mediate neuroinflammation and neurodegeneration following exposure to hypoxic-ischemic insults. Therefore, inhibition of the complement activation cascade may represent a potential therapeutic strategy for the management of ischemic brain injury. Decay-accelerating factor (DAF, also known as CD55) inhibits complement activation by suppressing the function of C3/C5 convertases, thereby limiting local generation or deposition of C3a/C5a and membrane attack complex (MAC or C5b-9) production. The present study investigates the ability of DAF to protect primary cultured neuronal cells subjected to sodium cyanide (NaCN)-induced hypoxia from degeneration and apoptosis.MethodsCultured primary cortical neurons from embryonic Sprague-Dawley rats were assigned one of four groups: control, DAF treatment alone, hypoxic, or hypoxic treated with DAF. Hypoxic cultures were exposed to NaCN for 1 hour, rinsed, followed by 24 hour exposure to 200 ng/ml of recombinant human DAF in normal medium. Human DAF was used in the present study and it has been shown to effectively regulate complement activation in rats. Neuronal cell function, morphology and viability were investigated by measuring plateau depolarization potential, counting the number dendritic spines, and observing TUNEL and MTT assays. Complement C3, C3a, C3a receptor (R) production, C3a-C3aR interaction and MAC formation were assessed along with the generation of activated caspase-9, activated caspase-3, and activated Src.ResultsWhen compared to controls, hypoxic cells had fewer dendritic spines, reduced plateau depolarization accompanied by increased apoptotic activity and accumulation of MAC, as well as up-regulation of C3, C3a and C3aR, enhancement of C3a-C3aR engagement, and elevated caspase and Src activity. Treatment of hypoxic cells with 200 ng/ml of recombinant human DAF resulted in attenuation of neuronal apoptosis and exerted significant protection against neuronal dendritic spine loss and plateau depolarization reduction. Furthermore, treatment with DAF resulted in decreased accumulation of C3a, MAC, C3a-C3aR interaction, caspase-9, activated caspase-3, and pTyr416-Src (activated Src) tyrosine kinase.ConclusionDAF was found to reduce neuronal cell death and apoptosis in NaCN induced hypoxia. This effect is attributed to the ability of DAF to limit complement activation and inhibit the activity of Src and caspases 9 and 3. This study supports the inhibiting of complement as a neuroprotective strategy against CNS ischemia/reperfusion injury.

show abstract

Expression of complement regulators and receptors on human NT2-N neurons—Effect of hypoxia and reoxygenation

Cited by 28 publications

References 37 publications

Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression

Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression

Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke

Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury

Contact Info

Product

Resources

About