Intracerebroventricular Administration of 192IgG-Saporin Alters the State of Microglia in the Neocortex

Volobueva, Maria N; Dobryakova, Yu. V.; Manolova, Anna; Stepanichev, M. Yu.; Kvichansky, A. A.; Gulyaeva, N. V.; Markevich, V A; Bolshakov, A D

doi:10.1134/s1819712420010213

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…Data of transcriptomic analysis were further supported by the results of real-time PCR [124]. Microglia activation could also be detected in the neocortex [133]. Taken together these data indicate that loss of cholinergic projections to the hippocampus leads to proliferation of microglia cells with phagocytic activity in the hippocampus; however, these cells do not express typical proinflammatory signaling molecules.…”

Section: Alzheimer's Diseasementioning

confidence: 67%

Saporin from Saponaria officinalis as a Tool for Experimental Research, Modeling, and Therapy in Neuroscience

Bolshakov

Stepanichev

Dobryakova

et al. 2020

Toxins

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Saporin, which is extracted from Saponaria officinalis, is a protein toxin that inactivates ribosomes. Saporin itself is non-selective toxin but acquires high specificity after conjugation with different ligands such as signaling peptides or antibodies to some surface proteins expressed in a chosen cell subpopulation. The saporin-based conjugated toxins were widely adopted in neuroscience as a convenient tool to induce highly selective degeneration of desired cell subpopulation. Induction of selective cell death is one of approaches used to model neurodegenerative diseases, study functions of certain cell subpopulations in the brain, and therapy. Here, we review studies where saporin-based conjugates were used to analyze cell mechanisms of sleep, general anesthesia, epilepsy, pain, and development of Parkinson’s and Alzheimer’s diseases. Limitations and future perspectives of use of saporin-based toxins in neuroscience are discussed.

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Section: Alzheimer's Diseasementioning

confidence: 67%

Saporin from Saponaria officinalis as a Tool for Experimental Research, Modeling, and Therapy in Neuroscience

Bolshakov

Stepanichev

Dobryakova

et al. 2020

Toxins

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“…To analyze the role played by septal cholinergic afferents in the regulation of gene expression in the hippocampus, we used intraseptal injection of the immunotoxin 192IgG-saporin. However, we previously showed that intracerebroventricular injection of 192IgG-saporin affects the functioning of the dorsal hippocampus [ 7 ] and some neocortical areas [ 15 ] and practically does not influence gene expression in the ventral hippocampus [ 7 ]. Therefore, our first step was to examine changes in the expression of genes in the dorsal hippocampus after induction of a cholinergic deficit by intraseptal injection of 192IgG-saporin.…”

Section: Resultsmentioning

confidence: 99%

The Induction of Long-Term Potentiation by Medial Septum Activation under Urethane Anesthesia Can Alter Gene Expression in the Hippocampus

Dobryakova,

Gerasimov,

Spivak

et al. 2023

IJMS

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We studied changes in the expression of early genes in hippocampal cells in response to stimulation of the dorsal medial septal area (dMSA), leading to long-term potentiation in the hippocampus. Rats under urethane anesthesia were implanted with stimulating electrodes in the ventral hippocampal commissure and dMSA and a recording electrode in the CA1 area of the hippocampus. We found that high-frequency stimulation (HFS) of the dMSA led to the induction of long-term potentiation in the synapses formed by the ventral hippocampal commissure on the hippocampal CA1 neurons. One hour after dMSA HFS, we collected the dorsal and ventral hippocampi on both the ipsilateral (damaged by the implanted electrode) and contralateral (intact) sides and analyzed the expression of genes by qPCR. The dMSA HFS led to an increase in the expression of bdnf and cyr61 in the ipsilateral hippocampi and egr1 in the ventral contralateral hippocampus. Thus, dMSA HFS under the conditions of degeneration of the cholinergic neurons in the medial septal area prevented the described increase in gene expression. The changes in cyr61 expression appeared to be dependent on the muscarinic M1 receptors. Our data suggest that the induction of long-term potentiation by dMSA activation enhances the expression of select early genes in the hippocampus.

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“…These data are in accordance with our previous study, which was performed using rLV-based vectors to transduce neurons with the Ngf gene ( Dobryakova et al, 2021 ). In the previous study, we used a model of cholinergic deficit induced by intracerebroventricular injection of 192IgG-saporin, which is associated with strong inflammation in the hippocampus ( Dobryakova et al, 2019 ) and neocortex ( Volobueva et al, 2020 ). We also observed beneficial effect of NGF in different behavioral tests, and here, we extend these findings using a model of cholinergic deficit, which is not associated with development of hippocampal inflammation.…”

Section: Discussionmentioning

confidence: 99%

Intrahippocampal Adeno-Associated Virus–Mediated Overexpression of Nerve Growth Factor Reverses 192IgG-Saporin–Induced Impairments of Hippocampal Plasticity and Behavior

et al. 2021

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One of the aspects of Alzheimer disease is loss of cholinergic neurons in the basal forebrain, which leads to development of cognitive impairment. Here, we used a model of cholinergic deficit caused by immunotoxin 192IgG-saporin to study possible beneficial effects of adeno-associated virus (AAV)–mediated overexpression of nerve growth factor (NGF) in the hippocampus of rats with cholinergic deficit. Suspension of recombinant AAV carrying control cassette or cassette with NGF was injected into both hippocampi of control rats or rats with cholinergic deficit induced by intraseptal injection of 192IgG-saporin. Analysis of choline acetyltransferase (ChAT) immunostaining showed that NGF overexpression in the hippocampus did not prevent strong loss of ChAT-positive neurons in the septal area caused by the immunotoxin. Induction of cholinergic deficit in the hippocampus led to impairments in Y-maze and beam-walking test but did not affect behavioral indices in the T-maze, open field test, and inhibitory avoidance training. NGF overexpression in the rats with cholinergic deficit restored normal animal behavior in Y-maze and beam-walking test. Recording of field excitatory postsynaptic potentials in vivo in the hippocampal CA1 area showed that induction of cholinergic deficit decreased magnitude of long-term potentiation (LTP) and prevented a decrease in paired-pulse ratio after LTP induction, and NGF overexpression reversed these negative changes in hippocampal synaptic characteristics. The beneficial effect of NGF was not associated with compensatory changes in the number of cells that express NGF receptors TrkA and NGFR in the hippocampus and medial septal area. NGF overexpression also did not prevent a 192IgG-saporin–induced decrease in the activity of acetylcholine esterase in the hippocampus. We conclude that NGF overexpression in the hippocampus under conditions of cholinergic deficit induces beneficial effects which are not related to maintenance of cholinergic function.

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Intracerebroventricular Administration of 192IgG-Saporin Alters the State of Microglia in the Neocortex

Cited by 4 publications

References 11 publications

Saporin from Saponaria officinalis as a Tool for Experimental Research, Modeling, and Therapy in Neuroscience

Saporin from Saponaria officinalis as a Tool for Experimental Research, Modeling, and Therapy in Neuroscience

The Induction of Long-Term Potentiation by Medial Septum Activation under Urethane Anesthesia Can Alter Gene Expression in the Hippocampus

Intrahippocampal Adeno-Associated Virus–Mediated Overexpression of Nerve Growth Factor Reverses 192IgG-Saporin–Induced Impairments of Hippocampal Plasticity and Behavior

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