Memory impairment is one of the main complications of Alzheimer’s disease (AD). This condition can be induced by hyper-stimulation of N-Methyl-D-aspartate receptors (NMDARs) of glutamate in the hippocampus, which ends up to pyramidal neurons determination. The release of neurotransmitters relies on voltage-gated calcium channels (VGCCs) such as P/Q-types. Omega-lycotoxin-Gsp2671e (OLG1e) is a P/Q-type VGCC modulator with high affinity and selectivity. This bio-active small protein was purified and identified from the Lycosa praegrandis venom. The effect of this state-dependent low molecular weight P/Q-type calcium modulator on rats was investigated via glutamate-induced excitotoxicity by N-Methyl-D-aspartate. Also, Electrophysiological amplitude of field excitatory postsynaptic potentials (fEPSPs) in the input–output and Long-term potentiation (LTP) curves were recorded in mossy fiber and the amount of synaptophysin (SYN), synaptosomal-associated protein, 25 kDa (SNAP-25), and synaptotagmin 1(SYT1) genes expression were measured using Real-time PCR technique for synaptic quantification. The outcomes of the current study suggest that OLG1e as a P/Q-type VGCC modulator has an ameliorative effect on excitotoxicity-induced memory defects and prevents the impairment of pyramidal neurons in the rat hippocampus.

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with amyloid-beta (Aβ) plaque formation and oxidative stress in the brain. Ghrelin has been proven to exert antioxidant activity and neuroprotection in different neurological diseases. This study is going on to examine the effect of ghrelin on antioxidant status in the rat’s model of AD induced by Aβ. Cognitive impairment was induced by intra-hippocampal administration of Aβ (10 μg) in Wistar rats and ghrelin (80 μg/kg) was administrated intraperitoneal for ten consecutive days. Behavior was assessed with Morris water maze and passive avoidance tests. Malondialdehyde (MDA) level as a marker of lipid peroxidation was assessed using the thiobarbituric acid. Catalase activity was assayed by the decomposition of H 2 O 2 . Antioxidant capacity was determined using the FRAP method. Treatment with ghrelin decreased the hippocampus and serum MDA levels in wild-type rodents and prevented an increase in hippocampal and serum MDA levels in animals receiving Aβ. There was no significant change in the serum catalase activity between the studied groups. Hippocampus catalase activity was reduced in the Aβ group and treatment with ghrelin increased it. The antioxidant capacity of the hippocampus and serum increased in the ghrelin-receiving control group. The hippocampus antioxidant capacity level decreased in the Aβ group, and treatment with ghrelin increased it, but there were no significant changes in the serum antioxidant capacity of animals receiving Aβ. These results provide evidence that the administration of ghrelin has antioxidant properties and protects against hippocampal lipid peroxidation in a rat model of AD.

SummaryBackgroundSerum small dense LDL-cholesterol (sdLDL-C) value is suggested to bean important risk factor for atherosclerosis. Since sdLDL-C changes may be related to PCSK9 and SREBP-2 functions, the aim of this study was to investigate correlations between sdLDL-C, circulating PCSK9, SREBP-2 expression and some lipid parameters in serum and butty coat fraction of healthy subjects.MethodsOne hundred and twenty-four subjects were randomly included in the study. The lipid profile was measured using routine laboratory methods. The serum sdLDL-C level was calculated by a heparin-related precipitation technique. The cellular LDL-C/protein and cholesterol/protein values were measured after lysing of cells with methanol/chloroform binary solvent. The circulating PCSK9 level was measured using ELISA technique. The SREBP-2 expression level was estimated using theRT-qPCR technique.ResultsData showed significant correlations between LDL-C, TG and sdLDL-C levels (r=0.34, p=0.001; r=0.2, p=0.04). The circulating PCSK9 level was correlated to LDL-C (r=0.29, p=0.04), but not to sdLDL-C (r=-0.08, p=0.57). Also, cellular LDL-C value was not related to serum LDL-C level (r=-0.12, p=0.39). Furthermore, there was an inverse correlation between cellular LDL-C/protein value and estimated de novo cholesterol/protein value (r= -0.5, p=0.001). Similar results were observed for cellular LDL-C/protein value and SREBP-2 expression level (r= -0.52, p=0.004).ConclusionsWe concluded that the serum sdLDL-C value is not related to circulating PCSK9. Furthermore, SREBP-2 regulatory system was able to elevate the cellular cholesterol level after reducing LDL influx. We suggest to investigate the cellular sdLDL fate and lipid synthesis pathways in PCSK9-targeting studies.

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Background. Cholesterol homeostasis is dependent upon the sterol regulatory element binding protein 2 (SREBP-2) regulatory system and the functioning of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9). Many studies have also reported that low density lipoprotein receptor (LDLR) levels in cellular membranes are related to the functioning of these proteins.