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

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)–me...

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Autores principales:	Yulia V. Dobryakova, Yulia S. Spivak, Maria I. Zaichenko, Alena A. Koryagina, Vladimir A. Markevich, Mikhail Yu. Stepanichev, Alexey P. Bolshakov
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	nerve growth factor 192IgG-saporin behavior long-term potentiation septum hippocampus Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/5eddee55a8b549fe98ce6f3db2e8bfe3
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spelling	oai:doaj.org-article:5eddee55a8b549fe98ce6f3db2e8bfe32021-11-15T06:34:56ZIntrahippocampal Adeno-Associated Virus–Mediated Overexpression of Nerve Growth Factor Reverses 192IgG-Saporin–Induced Impairments of Hippocampal Plasticity and Behavior1662-453X10.3389/fnins.2021.745050https://doaj.org/article/5eddee55a8b549fe98ce6f3db2e8bfe32021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.745050/fullhttps://doaj.org/toc/1662-453XOne 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.Yulia V. DobryakovaYulia S. SpivakMaria I. ZaichenkoAlena A. KoryaginaVladimir A. MarkevichMikhail Yu. StepanichevAlexey P. BolshakovFrontiers Media S.A.articlenerve growth factor192IgG-saporinbehaviorlong-term potentiationseptumhippocampusNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nerve growth factor 192IgG-saporin behavior long-term potentiation septum hippocampus Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	nerve growth factor 192IgG-saporin behavior long-term potentiation septum hippocampus Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Yulia V. Dobryakova Yulia S. Spivak Maria I. Zaichenko Alena A. Koryagina Vladimir A. Markevich Mikhail Yu. Stepanichev Alexey P. Bolshakov Intrahippocampal Adeno-Associated Virus–Mediated Overexpression of Nerve Growth Factor Reverses 192IgG-Saporin–Induced Impairments of Hippocampal Plasticity and Behavior
description	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.
format	article
author	Yulia V. Dobryakova Yulia S. Spivak Maria I. Zaichenko Alena A. Koryagina Vladimir A. Markevich Mikhail Yu. Stepanichev Alexey P. Bolshakov
author_facet	Yulia V. Dobryakova Yulia S. Spivak Maria I. Zaichenko Alena A. Koryagina Vladimir A. Markevich Mikhail Yu. Stepanichev Alexey P. Bolshakov
author_sort	Yulia V. Dobryakova
title	Intrahippocampal Adeno-Associated Virus–Mediated Overexpression of Nerve Growth Factor Reverses 192IgG-Saporin–Induced Impairments of Hippocampal Plasticity and Behavior
title_short	Intrahippocampal Adeno-Associated Virus–Mediated Overexpression of Nerve Growth Factor Reverses 192IgG-Saporin–Induced Impairments of Hippocampal Plasticity and Behavior
title_full	Intrahippocampal Adeno-Associated Virus–Mediated Overexpression of Nerve Growth Factor Reverses 192IgG-Saporin–Induced Impairments of Hippocampal Plasticity and Behavior
title_fullStr	Intrahippocampal Adeno-Associated Virus–Mediated Overexpression of Nerve Growth Factor Reverses 192IgG-Saporin–Induced Impairments of Hippocampal Plasticity and Behavior
title_full_unstemmed	Intrahippocampal Adeno-Associated Virus–Mediated Overexpression of Nerve Growth Factor Reverses 192IgG-Saporin–Induced Impairments of Hippocampal Plasticity and Behavior
title_sort	intrahippocampal adeno-associated virus–mediated overexpression of nerve growth factor reverses 192igg-saporin–induced impairments of hippocampal plasticity and behavior
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5eddee55a8b549fe98ce6f3db2e8bfe3
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Intrahippocampal Adeno-Associated Virus–Mediated Overexpression of Nerve Growth Factor Reverses 192IgG-Saporin–Induced Impairments of Hippocampal Plasticity and Behavior

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