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.

Excitotoxicity is a common pathological process in Alzheimer’s disease (AD) which is caused by the over-activity of N-Methyl-D-Aspartate receptors (NMDARs). The release of neurotransmitters depends on the activity of voltage-gated calcium channels (VGCCs). Hyper-stimulation of NMDARs can enhance the releasement of neurotransmitters through the VGCCs. This malfunction of channels can be blocked by selective and potent N-type VGCCs ligand. Under excitotoxicity condition, glutamate has negative effects on the pyramidal cells of the hippocampus, which ends in synaptic loss and elimination of these cells. These events leads to learning and memory elimination through the hippocampus circuit’s dysfunction. A suitable ligand has a high affinity to receptor or channel and is selective for its target. The bioactive small proteins of venom have these characteristics. Therefore, peptides and small proteins of animal venom are precious sources for pharmacological applications. The omega-agatoxin-Aa2a was purified, and identified from Agelena labyrinthica specimens, as an N-type VGCCs ligand for this study. The effect of the omega-agatoxin-Aa2a on the glutamate-induced excitotoxicity in rats was evaluated through behavioral tests including Morris Water Maze, and Passive avoidance. The syntaxin1A (SY1A), synaptotagmin1 (SYT1), and synaptophysin (SYN) genes expression were measured via Real-Time PCR. The local expression of synaptosomal-associated protein, 25 k Da (SNAP-25) was visualized using an immunofluorescence assay for synaptic quantification. Electrophysiological amplitude of field excitatory postsynaptic potentials (fEPSPs) in the input–output and LTP curves of mossy fiber were recorded. The cresyl violet staining of hippocampus sections was performed for the groups. Our results demonstrated that the omega-agatoxin-Aa2a treatment could recover the learning, and memory impairment caused by NMDA-induced excitotoxicity in 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.

Background: Excitotoxicity is a common pathological process in neurodegenerative diseases associated with overactivity of N-methyl-D-aspartate (NMDA) and P/Q type voltage-gated calcium (Cav2.1) channels. Omega-lycotoxin-Gsp2671g is a therapeutic tool to modulate overactive Cav2.1 (P/Q type) channels. Omega-lycotoxin binds to Cav2.1 channels with high affinity and selectivity. This study aimed to investigate the effects of Omega-lycotoxin on the cognitive impairment induced by kainic acid in rats. Methods: The effect of pre-treatment and post-treatment trials of intra-hippocampal Cornu Ammonis-3 administration of omega-lycotoxin (0.5, 1 or 2µg) was studied on the cognitive impairment induced by kainic acid in rats. The rats’ learning and memory were assessed by the passive avoidance and a single-day testing version of the Morris water maze method. Results: Omega-lycotoxin caused a significant increase in the latency of the passive avoidance test and the duration of their presence in the target area of the Morris water maze test compared to the groups treated with kainic acid (P<0.0001). There were statistically significant differences for the effects of various doses of omega-lycotoxin. The post-treatment groups showed a greater improvement than those in the pretreatment groups. Conclusion: The findings demonstrated that a single dose of omega-lycotoxin can prevent or revert the memory impairment caused by kainic acid in rats.

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