Differential expression of serum biomarkers in hemodialysis patients with mild cognitive decline: A prospective single-center cohort study.

Studies suggest that hemodialysis patients are at a higher risk for cognitive decline than healthy individuals; however, underlying mechanisms have not been fully elucidated. We aimed to investigate the roles of serum biomarkers, such as brain-derived neurotrophic factor (BDNF), inflammatory cytokines, fibroblast growth factor (FGF)-23 and its co-receptor α-klotho and platelet (PLT) count in mild cognitive decline (MCD) of patients undergoing hemodialysis in this prospective cohort study. Serum levels of BDNF, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and the number of PLT were significantly altered in the MCD group compared with those in healthy controls (HCs) or those with normal cognitive function (NCF). Although serum α-klotho and FGF-23 levels were significantly altered in the MCD group, there were no statistical differences between the MCD and NCF groups. Serum BDNF levels and PLT counts were significantly correlated with cognitive test scores. Receiver operating characteristic (ROC) curves demonstrated that BDNF and PLT were potential biomarkers for improved MCD diagnosis in patients with hemodialysis. These findings suggest that hemodialysis-related MCD is associated with altered BDNF, TNF-α and IL-6 levels as well as PLT counts and that serum BDNF levels and PLT counts are potential biomarkers for hemodialysis-related MCD diagnosis.

Adenosine monophosphate-activated protein kinase activation mediates the leptin-induced attenuation of cognitive impairment in a streptozotocin-induced rat model.

Several lines of evidence have shown that the incidence of cognitive impairment in diabetic patients is significantly higher than that in healthy individuals, but the exact pathogenesis has not been fully elucidated. Furthermore, it has been suggested that leptin may have a therapeutic effect in cognitive dysfunction. The aim of the present study was to observe the effect of leptin on cognitive dysfunction in streptozotocin (STZ)-induced diabetic rats, and to explore whether adenosine monophosphate-activated protein kinase (AMPK) activation was involved in any potential therapeutic effect of leptin. Compared with control rats, STZ rats exhibited decreased levels of AMPK and a poor performance in the Morris water maze, while these changes were reversed by leptin. Furthermore, Compound C, an AMPK antagonist, significantly attenuated the leptin-induced cognitive function improvement in the STZ rats. In conclusion, these results suggest that AMPK activation may play a critical role in the leptin-induced attenuation of STZ-induced cognitive impairment.

Effects of BD1047, a σ1 receptor antagonist, on the expression of mTOR, Camk2γ and GSK-3ß in fluvoxamine-treated N2a cells.

Fluvoxamine, a common antidepressant agent, is designed to exert its pharmacological effect by inhibiting synaptic serotonin reuptake. However, increasing evidence has demonstrated that σ1 receptors are likely to be involved in the mechanism of action of fluvoxamine. The present study aimed to observe the effects of fluvoxamine on the expression levels of mammalian target of rapamycin (mTOR), Ca2+/calmodulin-dependent protein kinase 2γ (Camk2γ) and glycogen synthase kinase-3ß (GSK-3ß) in fluvoxamine-treated N2a cells and attempted to elucidate whether σ1 receptors mediate the pharmacological effects of fluvoxamine. The N2a cells were randomly divided into three groups (each n=6): DMEM group (D group), 0.5 µmol/l fluvoxamine group (F group) and 0.2 µmol/l BD1047 (a σ1 receptor antagonist) + 0.5 µmol/l fluvoxamine group (BF group). Western blotting was used to determine the expression levels of mTOR, Camk2γ and GSK-3ß in the cultured N2a cells after two days of incubation. The F group exhibited significant increases in the expression levels of mTOR and Camk2γ and a significant reduction in the expression levels of GSK-3ß compared with those in the D group (P<0.01). By contrast, the BF group demonstrated significant reductions in the expression levels of mTOR and Camk2γ and a significant increase in the expression levels of GSK-3ß, compared with those in the F group (P<0.01). These results suggest that σ1 receptors mediate fluvoxamine-elicited changes in the expression levels of mTOR, Camk2γ and GSK-3ß in N2a cells, which indicates that σ1 receptors are likely to be involved in the pharmacological effects of fluvoxamine.

Ketamine attenuates the lipopolysaccharide-induced inflammatory response in cultured N2a cells.

The use of ketamine is recommended in patients with sepsis undergoing surgery due to its anti-inflammatory effects. However, a paucity of data exists with regard to the anti-inflammatory effects of ketamine in the central nervous system. Therefore, the present study aimed to investigate the effect of ketamine on lipopolysaccharide (LPS)­induced inflammatory responses in cultured Neuro2a (N2a) cells and to elucidate its potential mechanism of action. N2a cells were randomly divided into the following 3 groups (n=6): The DMEM culture solution administration alone group, the 0.5 µmol/l LPS administration alone group and the 1 µmol/l ketamine plus 0.5 µmol/l LPS administration group. The expression levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB and inducible nitric oxide synthase (iNOS) were determined. LPS-treated N2a cells exhibited a significant increase in the expression levels of IL-1ß, IL-6, TNF-α, NF-κB and iNOS, while the administration of ketamine eliminated the LPS-induced production of IL-1ß, IL-6, TNF-α, NF-κB and iNOS. Based on our data, we hypothesized that the anti-inflammatory effect exerted by ketamine on N2a cells was potentially due to the inhibition of NF-κB and iNOS.