Ameliorative effects of omega-lycotoxin-Gsp2671e purified from the spider venom of Lycosa praegrandis on memory deficits of glutamate-induced excitotoxicity rat model

Abstract

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.

Alleviation of cognitive deficits in a rat model of glutamate-induced excitotoxicity, using an N-type voltage-gated calcium channel ligand, extracted from Agelena labyrinthica crude venom

“…Our data indicated that administration of NMDA in rat hippocampus could induces excitotoxicity due to over-stimulation of NMDARs, which in turn reduces SNAP-25 expression protein level. Also, this administration reduced SY1A, SYT1, and SYN mRNAs expression (Yu et al, 2006;Li et al, 2012;You et al, 2018;Keimasi et al, 2022). This reduction of SNAP-25, SY1A, SYT1, and SYN leads to cognitive impairment and memory dysfunction, which can be reversed by an increase in SNAP-25, SY1A, SYT1, and SYN following the blockage of presynaptic N-type VGCCs with omega-agatoxin-Aa2a.…”

“…Therefore, a decrease in the potency of each part of a venom following separation of crude venom seems logical. On the other hand, the enzymatic part of a crude venom has a high molecular weight whereas; the omega-agatoxin-Aa2a protein has a low molecular weight (Keimasi et al, 2022). Accordingly, the omega-agatoxin-Aa2a protein is safe, particularly in the microliter concentration, which has been used in the current study.…”

“…The desired peak was re-injected into the device to ensure purity, and the result was presented the collected fraction was subjected to 12% SDS-PAGE. The selected peak obtained from this method project into HPLC-ESI-MS (Keimasi et al, 2022).…”

“…The rats (six in each group) were anesthetized with urethane (1.5 g/kg; intraperitoneal injection) dissolved in 0.9% normal saline solution. The surgery and LTP recording procedures from the hippocampal CA 3 area were executed as formerly has been described by Keimasi et al (2022).…”

The synergic effects of presynaptic calcium channel antagonists purified from spiders on memory elimination of glutamate-induced excitotoxicity in the rat hippocampus trisynaptic circuit

“…LTP plays a crucial role in increasing dendrites and synaptic plasticity in the brain ( Bin Ibrahim et al, 2022 ). Overstimulation of these receptors by agonists, such as NMDA, glutamate, aspartate, and kainic acid, can lead to destructive reactions in neuronal cells ( Jarrard, 2002 ; Zhang et al, 2014 ; Hosseini-Sharifabad et al, 2021 ; Keimasi et al, 2022 ; Keimasi et al, 2023a ). This hyper-stimulation may be due to the over-activity of the presynaptic voltage-gated calcium channels (VGCCs), which are involved in glutamate release ( Schurr, 2004 ; Nimmrich and Gross, 2012 ; Sousa et al, 2013 ; Mochida, 2019 ).…”