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

The hippocampus is a complex area of the mammalian brain and is responsible for learning and memory. The trisynaptic circuit engages with explicit memory. Hippocampal neurons express two types of presynaptic voltage-gated calcium channels (VGCCs) comprising N and P/Q-types. These VGCCs play a vital role in the release of neurotransmitters from presynaptic neurons. The chief excitatory neurotransmitter at these synapses is glutamate. Glutamate has an essential function in learning and memory under normal conditions. The release of neurotransmitters depends on the activity of presynaptic VGCCs. Excessive glutamate activity, due to either excessive release or insufficient uptake from the synapse, leads to a condition called excitotoxicity. This pathological state is common among all neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. Under these conditions, glutamate adversely affects the trisynaptic circuitry, leading to synaptic destruction and loss of memory and learning performance. This study attempts to clarify the role of presynaptic VGCCs in memory performance and reveals that modulating the activity of presynaptic calcium channels in the trisynaptic pathway can regulate the excitotoxic state and consequently prevent the elimination of neurons and synaptic degradation. All of these can lead to an improvement in learning and memory function. In the current study, two calcium channel blockers-omega-agatoxin-Aa2a and omega-Lsp-IA-were extracted, purified, and identified from spiders (Agelena orientalis and Hogna radiata) and used to modulate N and P/Q VGCCs. The effect of omega-agatoxin-Aa2a and omega-Lsp-IA on glutamate-induced excitotoxicity in rats was evaluated using the Morris water maze task as a behavioral test. The local expression of synaptophysin (SYN) was visualized for synaptic quantification using an immunofluorescence assay. The electrophysiological amplitudes of the field excitatory postsynaptic potentials (fEPSPs) in the input-output and LTP curves of the mossy fiber and Schaffer collateral circuits were recorded. The results of our study demonstrated that N and P/Q VGCC modulation in the hippocampus trisynaptic circuit of rats with glutamate-induced excitotoxicity dysfunction could prevent the destructive consequences of excitotoxicity in synapses and improve memory function and performance.

Purified Native Protein Extracted from the Venom of Agelena orientalis Attenuates Memory Defects in the Rat Model of Glutamate-Induced Excitotoxicity.

Spider venom contains various peptides and proteins, which can be used for pharmacological applications. Finding novel therapeutic strategies against neurodegenerative diseases with the use of purified peptides and proteins, extracted from spiders can be greatly precious. Neurodegenerative diseases are rapidly developing and expanding all over the world. Excitotoxicity is a frequent condition amongst neuro-degenerative disorders. This harmful process is usually induced through hyper-activation of N-Methyl-D-Aspartate (NMDA) receptor, and P/Q-type voltage-gated calcium channels (VGCCs). The omega-agatoxin-Aa4b is a selective and strong VGCCblocker. This study aimed to investigate the effects of this blocker on the NMDA-induced memory and learning defect in rats. For this purpose, nineteen spiders of the funnel-weaver Agelena orientalis species were collected. The extracted venom was lyophilized andpurified through gel-filtration chromatography, and capillary electrophoresis techniques. Subsequently, mass spectrometry (HPLC-ESI-MS) was used for identification of this bio-active small protein. Afterward, the effect of the omega-agatoxin-Aa4b (2 µg, intra-cornu ammonis-3 of the hippocampus) on the NMDA-induced learning and memory deficits in rats was evaluated. Learning and memory performances were evaluated by the use of passive avoidance test. For synaptic quantification and memory function the amount of calcium/calmodulin-dependent protein kinase ІІ (CaCdPKІІ) gene expression was measured using the Real-time PCR technique. To compare the experimental groups, hematoxylin and eosin (H&E) staining of hippocampus tissues was performed. Our results rendered that the omega-Agatoxin-Aa4b treatment can ameliorate and reverse the learning and memory impairment caused by NMDA-induced excitotoxicity in rat hippocampus.

Corrigendum: 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.

[This corrects the article DOI: 10.3389/fnmol.2023.1123343.].

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.

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.

Taxonomic revision of the troglophile Spariolenus spiders (Araneae: Sparassidae) in South and West Asia.

The taxonomy of the genus Spariolenus Simon, 1880 (Heteropodinae) is updated in its entire distribution range in South and West Asia. Newly collected specimens and historical museum material were studied, some date back to more than 124 years. Four new species are described as Spariolenus omidvarbrothers sp. n. (male, female) from southeastern Iran, S. baluchistanicus sp. n. (female) from Pakistan and, S. bakasura sp. n. (male, female) and S. kabandha sp. n. (female) from the Western Ghats and northern regions of India, respectively; specimens of the latter three species had been previously incorrectly identified as S. tigris Simon, 1880. Spariolenus lindbergi (Roewer, 1962) comb. nov. is transferred from the genus Heteropoda Latreille, 1804. We discovered and described its male for the first time, along with redescription of the female using recently collected material near the type locality from Afghanistan. Two species, Spariolenus mansourii Moradmand, 2017 (Iran) and S. secundus Jger, 2006 (Oman) are recorded from new geographic localities. A distribution map of all extant Spariolenus species with updated records is presented.

Ecological niche modelling and climate change in two species groups of huntsman spider genus Eusparassus in the Western Palearctic.

The huntsman spiders' genus Eusparassus are apex arthropod predators in desert ecosystems of the Afrotropical and Palearctic ecoregions. The Eusparassus dufouri and E. walckenaeri clades are two distinct taxonomic, phylogenetic, and geographic units concerning morphology, molecular phylogeny, and spatial data; but little is known about their ecological niche. We applied the maximum-entropy approach and modelled ecologic niches of these two phylogenetically closely related clades. Ecological niches of the two clades were compared using identity and background tests and two different metrics, the Schooner's D and Warren's I. We also predicted the impacts of climate change on the distribution of the two clades. The results of the identity test showed that the ecological niches of the two clades were different in geographic space but were similar in environmental space. While results of the background test revealed that the ecological niches of the two clades were similar in geographic and environmental space. This indicated that "niche conservatism" had an important role over the evolutionary time of allopatric diversification. However, the normalized difference vegetation index vs. topographic heterogeneity had influenced the niches of the dufouri and walckenaeri clades, respectively. The analyses recovered that the two clades' climatically suitable habitats will increase under future climate (the year 2070). However, since the two clades are characterized by the narrow range of environmental optimum and the accordingly high limits of tolerance, they are vulnerable to climate change.

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

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.

New insights to the taxonomy of Rhagodes eylandti (Walter, 1889): A remarkable sexually dimorphic species (Solifugae: Rhagodidae).

The taxonomy of the widespread camel spider, Rhagodes eylandti (Walter, 1889), is herein updated and revised by proposing three nominal taxa as its junior synonyms. These are based on data from males of two taxa, Rhagodes melanopygus nigricans Birula, 1905 and R. plumbescens (Walter, 1889), and a female of R. melanochaetus Heymons, 1902. Consequently, both sexes of R. eylandti are re-described and the validity of their morphological diagnostic characters is evaluated. Detailed morphological and morphometrical characters, as well as data on sexual dimorphism and intraspecific variations, are provided. The illustrations of type material are given for the first time. Moreover, a distribution map and ecological notes are presented.

A new Pardosa species from northern Iran (Araneae, Lycosidae).

A study of Pardosa pontica (Thorell, 1875) in Iran indicates two distinct morphospecies. A detailed comparison of these morphospecies and types of P. pontica reveals that populations from Mazandaran, Golestan and North Khorasan Provinces of Iran and Balkan Welaýaty of Turkmenistan belong to a newly described species, P. mirzakhaniae sp. n., and populations in western and easternmost Iran belong to P. pontica. Although the two morphospecies differ in colour, size and spination, no molecular differences in 16S rRNA and COI were detected.

On the genus Cebrennus Simon, 1880 in Iran with description of a new species from Iranian Central Desert (Araneae: Sparassidae).

The taxonomic knowledge on the desert-dwelling sparassid genus Cebrennus Simon, 1880 in Iran is updated by describing a new species, Cebrennus rambodjavani sp. nov. (male) from northern Qom in Iran's Central Desert, and reviewing the material of the previous Iranian record of the genus [sub C. kochi (O. Pickard-Cambridge, 1872)] from Bushehr, southern Iran, which is found to be a misidentification. A revised definition of the term "embolus kink", a male copulatory structure in Cebrennus, is given. A comparative discussion of this structure between several representatives of the genus Cebrennus is included.

Molecular phylogeny of the spider family Sparassidae with focus on the genus Eusparassus and notes on the RTA-clade and 'Laterigradae'.

The phylogeny of the spider family Sparassidae is comprehensively investigated using four molecular markers (mitochondrial COI and 16S; nuclear H3 and 28S). Sparassidae was recovered as monophyletic and as most basal group within the RTA-clade. The higher-level clade Dionycha was not but monophyly of RTA-clade was supported. No affiliation of Sparassidae to other members of the 'Laterigradae' (Philodromidae, Selenopidae and Thomisidae) was observed, and the crab-like posture of this group assumed a result of convergent evolution. Only Philodromidae and Selenopidae were found members of a supported clade, but together with Salticidae and Corinnidae, while Thomisidae was nested within the higher Lycosoidea. Within Sparassidae monophyly of the subfamilies Heteropodinae sensu stricto, Palystinae and Deleninae was recovered. Sparianthinae was supported as the most basal clade within Sparassidae. Sparassinae and the genus Olios were found each to be polyphyletic. Eusparassinae was not recovered monophyletic, with the two original genera Eusparassus and Pseudomicrommata in separate clades and only the latter clustered with most other assumed Eusparassinae, here termed the "African clade". Further focus was on the monophyletic genus Eusparassus and its proposed species groups, of which the dufouri-, walckenaeri- and doriae-group were confirmed as monophyletic with the two latter groups more closely related. According to molecular clock analyses, the divergence time of Sparassidae and Eusparassus was estimated with 186 and 70 million years ago respectively.

The stone huntsman spider genus Eusparassus (Araneae: Sparassidae): systematics and zoogeography with revision of the African and Arabian species.

An overview on the systematics of the stone huntsman spider genus Eusparassus Simon, 1903 and an identification key to the known species are presented. Six species-groups are proposed: the walckenaeri group (3 species, Eastern Mediterranean to Arabia and parts of North-Eastern Africa), dufouri group (8 species, Iberian Peninsula to parts of North-western Africa), vestigator group (3 species, Central to Eastern Africa and an isolated area in India), jaegeri group (4 species, Southern and South-Eastern Africa), tuckeri group (2 species, South-Western Africa) and doriae group (7 species, Middle East to Central and South Asia). Two species, E. pontii Caporiacco, 1935 and E. xerxes (Pocock, 1901) could not be placed in any of the above groups. The species from Africa and Arabia are revised. The following ten species are re-described: Eusparassus barbarus (Lucas, 1846), E. atlanticus Simon, 1909 stat. nov., E. syrticus Simon, 1909, E. oraniensis (Lucas, 1846), E. letourneuxi (Simon, 1874), E. fritschi (Koch, 1873) stat. rev., E. walckenaeri (Audouin, 1826), E. vestigator (Simon, 1897) comb. nov., E. laevatus (Simon, 1897) comb. nov. and E. tuckeri (Lawrence, 1927) comb. nov. The latter three species are transferred from Olios Walckenaer, 1837. Seven new species are described: Eusparassus arabicus spec. nov. (male, female) from Arabian Peninsula, E. educatus spec. nov. (male, female) from Namibia, E. reverentia spec. nov. (male, female) from Burkina Faso and Nigeria, E. jaegeri spec. nov. (male, female) from South Africa and Botswana, E. jocquei spec. nov. (male, female) from Zimbabwe, E. borakalalo spec. nov. (female) from South Africa and E. schoem-anae spec. nov. (male, female) from South Africa and Namibia. Three taxa, E. dufouri maximus Strand, 1906 syn. nov., E. rufobrunneus Caporiacco, 1941 syn. nov. and Olios furcatus Lawrence, 1927 syn. nov. are proposed as junior syn-onyms of E. oraniensis, E. vestigator comb. nov. and E. tuckeri comb. nov. respectively. Males of E. atlanticus stat. nov. and E. fritschi stat. rev. are described for the first time as in the female of E. vestigator comb. nov. Neotypes are desig-nated for E. barbarus, E. oraniensis and E. letourneuxi (all from Algeria). The male and female of Cercetius perezi Simon, 1902, which was known only from the immature holotype, are described here for the first time. This resulted in recogniz-ing the monotypic and little used generic name Cercetius Simon, 1902 as a synonym of the widely used name Eusparas-sus. Nearly all the species are illustrated for the first time. Eusparassus concolor Caporiacco, 1939 is transferred to Olios and the replacement name Olios quesitio is proposed because of secondary homonymy. For the majority of the species, new geographical records are presented. The systematics and zoogeography of the currently known species and species groups are discussed. A brief note on the copulation process of E. walckenaeri is presented.