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Intracerebroventricular Administration of (192)IgG-Saporin Alters Expression of Microglia-Associated Genes in the Dorsal But Not Ventral Hippocampus

One of important aspects of development of Alzheimer’s disease is degeneration of septal cholinergic neurons that innervate the hippocampus. We took advantage of widely used model of cholinergic deficit in the hippocampus, intracerebroventricular administration of (192)IgG-saporin (Ig-saporin), to a...

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Autores principales: Dobryakova, Yulia V., Kasianov, Artem, Zaichenko, Maria I., Stepanichev, Mikhail Y., Chesnokova, Ekaterina A., Kolosov, Petr M., Markevich, Vladimir A., Bolshakov, Alexey P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5776139/
https://www.ncbi.nlm.nih.gov/pubmed/29386992
http://dx.doi.org/10.3389/fnmol.2017.00429
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author Dobryakova, Yulia V.
Kasianov, Artem
Zaichenko, Maria I.
Stepanichev, Mikhail Y.
Chesnokova, Ekaterina A.
Kolosov, Petr M.
Markevich, Vladimir A.
Bolshakov, Alexey P.
author_facet Dobryakova, Yulia V.
Kasianov, Artem
Zaichenko, Maria I.
Stepanichev, Mikhail Y.
Chesnokova, Ekaterina A.
Kolosov, Petr M.
Markevich, Vladimir A.
Bolshakov, Alexey P.
author_sort Dobryakova, Yulia V.
collection PubMed
description One of important aspects of development of Alzheimer’s disease is degeneration of septal cholinergic neurons that innervate the hippocampus. We took advantage of widely used model of cholinergic deficit in the hippocampus, intracerebroventricular administration of (192)IgG-saporin (Ig-saporin), to analyze the postponed consequences of cholinergic deficit in different parts of the hippocampus. We studied effects of the immunotoxin on the behavior of rats and gene expression in the dorsal and ventral hippocampus using RNA-seq approach. We found that under normal conditions dorsal and ventral parts of the hippocampus differ in the expression of 1129 protein-coding genes and 49 non-coding RNAs (ncRNAs) and do not differ in the expression of 10 microRNAs, which were detected in both parts of the hippocampus. Ig-saporin-induced degeneration of cholinergic septal neurons did not affect rat behavior in open field, T-maze, and passive avoidance task but impaired memory retention in Morris water maze. To analyze (192)Ig-saporin-induced changes in the gene expression, we formed the following groups of genes: genes expressed exclusively in certain cell types (neurons, astrocytes, microglia, oligodendrocytes, and vascular cells) and, among universally expressed genes, a group of genes that encode ribosome-forming proteins. For all groups of genes, the alterations in the gene expression produced by the immunotoxin were stronger in the dorsal as compared to the ventral hippocampus. We found that, among groups of universally expressed genes, Ig-saporin increased the expression of ribosome-forming proteins in both dorsal and ventral hippocampus. Ig-saporin also strongly upregulated expression of microglia-specific genes only in the dorsal hippocampus. A subset of affected microglial genes comprised genes associated with inflammation, however, did not include genes related to acute inflammation such as interleukins-1b, -6, -15, and -18 as well as TNF. The expression of other cell-specific genes (genes specific for neurons, astrocytes, oligodendrocytes, and vascular cells) was unaffected. The data obtained suggest that disturbance of memory-associated behavior after administration of Ig-saporin is associated with upregulation of microglia-associated genes in the dorsal but not ventral hippocampus.
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spelling pubmed-57761392018-01-31 Intracerebroventricular Administration of (192)IgG-Saporin Alters Expression of Microglia-Associated Genes in the Dorsal But Not Ventral Hippocampus Dobryakova, Yulia V. Kasianov, Artem Zaichenko, Maria I. Stepanichev, Mikhail Y. Chesnokova, Ekaterina A. Kolosov, Petr M. Markevich, Vladimir A. Bolshakov, Alexey P. Front Mol Neurosci Neuroscience One of important aspects of development of Alzheimer’s disease is degeneration of septal cholinergic neurons that innervate the hippocampus. We took advantage of widely used model of cholinergic deficit in the hippocampus, intracerebroventricular administration of (192)IgG-saporin (Ig-saporin), to analyze the postponed consequences of cholinergic deficit in different parts of the hippocampus. We studied effects of the immunotoxin on the behavior of rats and gene expression in the dorsal and ventral hippocampus using RNA-seq approach. We found that under normal conditions dorsal and ventral parts of the hippocampus differ in the expression of 1129 protein-coding genes and 49 non-coding RNAs (ncRNAs) and do not differ in the expression of 10 microRNAs, which were detected in both parts of the hippocampus. Ig-saporin-induced degeneration of cholinergic septal neurons did not affect rat behavior in open field, T-maze, and passive avoidance task but impaired memory retention in Morris water maze. To analyze (192)Ig-saporin-induced changes in the gene expression, we formed the following groups of genes: genes expressed exclusively in certain cell types (neurons, astrocytes, microglia, oligodendrocytes, and vascular cells) and, among universally expressed genes, a group of genes that encode ribosome-forming proteins. For all groups of genes, the alterations in the gene expression produced by the immunotoxin were stronger in the dorsal as compared to the ventral hippocampus. We found that, among groups of universally expressed genes, Ig-saporin increased the expression of ribosome-forming proteins in both dorsal and ventral hippocampus. Ig-saporin also strongly upregulated expression of microglia-specific genes only in the dorsal hippocampus. A subset of affected microglial genes comprised genes associated with inflammation, however, did not include genes related to acute inflammation such as interleukins-1b, -6, -15, and -18 as well as TNF. The expression of other cell-specific genes (genes specific for neurons, astrocytes, oligodendrocytes, and vascular cells) was unaffected. The data obtained suggest that disturbance of memory-associated behavior after administration of Ig-saporin is associated with upregulation of microglia-associated genes in the dorsal but not ventral hippocampus. Frontiers Media S.A. 2018-01-17 /pmc/articles/PMC5776139/ /pubmed/29386992 http://dx.doi.org/10.3389/fnmol.2017.00429 Text en Copyright © 2018 Dobryakova, Kasianov, Zaichenko, Stepanichev, Chesnokova, Kolosov, Markevich and Bolshakov. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Dobryakova, Yulia V.
Kasianov, Artem
Zaichenko, Maria I.
Stepanichev, Mikhail Y.
Chesnokova, Ekaterina A.
Kolosov, Petr M.
Markevich, Vladimir A.
Bolshakov, Alexey P.
Intracerebroventricular Administration of (192)IgG-Saporin Alters Expression of Microglia-Associated Genes in the Dorsal But Not Ventral Hippocampus
title Intracerebroventricular Administration of (192)IgG-Saporin Alters Expression of Microglia-Associated Genes in the Dorsal But Not Ventral Hippocampus
title_full Intracerebroventricular Administration of (192)IgG-Saporin Alters Expression of Microglia-Associated Genes in the Dorsal But Not Ventral Hippocampus
title_fullStr Intracerebroventricular Administration of (192)IgG-Saporin Alters Expression of Microglia-Associated Genes in the Dorsal But Not Ventral Hippocampus
title_full_unstemmed Intracerebroventricular Administration of (192)IgG-Saporin Alters Expression of Microglia-Associated Genes in the Dorsal But Not Ventral Hippocampus
title_short Intracerebroventricular Administration of (192)IgG-Saporin Alters Expression of Microglia-Associated Genes in the Dorsal But Not Ventral Hippocampus
title_sort intracerebroventricular administration of (192)igg-saporin alters expression of microglia-associated genes in the dorsal but not ventral hippocampus
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5776139/
https://www.ncbi.nlm.nih.gov/pubmed/29386992
http://dx.doi.org/10.3389/fnmol.2017.00429
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