Scavenging Tumor Necrosis Factor α Does Not Affect Inhibition of Dentate Granule Cells Following In Vitro Entorhinal Cortex Lesion

Neurons that lose part of their afferent input remodel their synaptic connections. While cellular and molecular mechanisms of denervation-induced changes in excitatory neurotransmission have been identified, little is known about the signaling pathways that control inhibition in denervated networks....

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Autores principales:	Dimitrios Kleidonas, Andreas Vlachos
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	entorhinal cortex lesion denervation TNFα microglia synaptic scaling inhibition Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8e656cda03fc4e4ba80c765bdb5426ea
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spelling	oai:doaj.org-article:8e656cda03fc4e4ba80c765bdb5426ea2021-11-25T17:13:07ZScavenging Tumor Necrosis Factor α Does Not Affect Inhibition of Dentate Granule Cells Following In Vitro Entorhinal Cortex Lesion10.3390/cells101132322073-4409https://doaj.org/article/8e656cda03fc4e4ba80c765bdb5426ea2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3232https://doaj.org/toc/2073-4409Neurons that lose part of their afferent input remodel their synaptic connections. While cellular and molecular mechanisms of denervation-induced changes in excitatory neurotransmission have been identified, little is known about the signaling pathways that control inhibition in denervated networks. In this study, we used mouse entorhino-hippocampal tissue cultures of both sexes to study the role of the pro-inflammatory cytokine tumor necrosis factor α (TNFα) in denervation-induced plasticity of inhibitory neurotransmission. In line with our previous findings in vitro, an entorhinal cortex lesion triggered a compensatory increase in the excitatory synaptic strength of partially denervated dentate granule cells. Inhibitory synaptic strength was not changed 3 days after the lesion. These functional changes were accompanied by a recruitment of microglia in the denervated hippocampus, and experiments in tissue cultures prepared from TNF-reporter mice [<i>C57BL/6-Tg(TNFa-eGFP)</i>] showed increased TNFα expression in the denervated zone. However, inhibitory neurotransmission was not affected by scavenging TNFα with a soluble TNF receptor. In turn, a decrease in inhibition, i.e., decreased frequencies of miniature inhibitory postsynaptic currents, was observed in denervated dentate granule cells of microglia-depleted tissue cultures. We conclude from these results that activated microglia maintain the inhibition of denervated dentate granule cells and that TNFα is not required for the maintenance of inhibition after denervation.Dimitrios KleidonasAndreas VlachosMDPI AGarticleentorhinal cortex lesiondenervationTNFαmicrogliasynaptic scalinginhibitionBiology (General)QH301-705.5ENCells, Vol 10, Iss 3232, p 3232 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	entorhinal cortex lesion denervation TNFα microglia synaptic scaling inhibition Biology (General) QH301-705.5
spellingShingle	entorhinal cortex lesion denervation TNFα microglia synaptic scaling inhibition Biology (General) QH301-705.5 Dimitrios Kleidonas Andreas Vlachos Scavenging Tumor Necrosis Factor α Does Not Affect Inhibition of Dentate Granule Cells Following In Vitro Entorhinal Cortex Lesion
description	Neurons that lose part of their afferent input remodel their synaptic connections. While cellular and molecular mechanisms of denervation-induced changes in excitatory neurotransmission have been identified, little is known about the signaling pathways that control inhibition in denervated networks. In this study, we used mouse entorhino-hippocampal tissue cultures of both sexes to study the role of the pro-inflammatory cytokine tumor necrosis factor α (TNFα) in denervation-induced plasticity of inhibitory neurotransmission. In line with our previous findings in vitro, an entorhinal cortex lesion triggered a compensatory increase in the excitatory synaptic strength of partially denervated dentate granule cells. Inhibitory synaptic strength was not changed 3 days after the lesion. These functional changes were accompanied by a recruitment of microglia in the denervated hippocampus, and experiments in tissue cultures prepared from TNF-reporter mice [<i>C57BL/6-Tg(TNFa-eGFP)</i>] showed increased TNFα expression in the denervated zone. However, inhibitory neurotransmission was not affected by scavenging TNFα with a soluble TNF receptor. In turn, a decrease in inhibition, i.e., decreased frequencies of miniature inhibitory postsynaptic currents, was observed in denervated dentate granule cells of microglia-depleted tissue cultures. We conclude from these results that activated microglia maintain the inhibition of denervated dentate granule cells and that TNFα is not required for the maintenance of inhibition after denervation.
format	article
author	Dimitrios Kleidonas Andreas Vlachos
author_facet	Dimitrios Kleidonas Andreas Vlachos
author_sort	Dimitrios Kleidonas
title	Scavenging Tumor Necrosis Factor α Does Not Affect Inhibition of Dentate Granule Cells Following In Vitro Entorhinal Cortex Lesion
title_short	Scavenging Tumor Necrosis Factor α Does Not Affect Inhibition of Dentate Granule Cells Following In Vitro Entorhinal Cortex Lesion
title_full	Scavenging Tumor Necrosis Factor α Does Not Affect Inhibition of Dentate Granule Cells Following In Vitro Entorhinal Cortex Lesion
title_fullStr	Scavenging Tumor Necrosis Factor α Does Not Affect Inhibition of Dentate Granule Cells Following In Vitro Entorhinal Cortex Lesion
title_full_unstemmed	Scavenging Tumor Necrosis Factor α Does Not Affect Inhibition of Dentate Granule Cells Following In Vitro Entorhinal Cortex Lesion
title_sort	scavenging tumor necrosis factor α does not affect inhibition of dentate granule cells following in vitro entorhinal cortex lesion
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8e656cda03fc4e4ba80c765bdb5426ea
work_keys_str_mv	AT dimitrioskleidonas scavengingtumornecrosisfactoradoesnotaffectinhibitionofdentategranulecellsfollowinginvitroentorhinalcortexlesion AT andreasvlachos scavengingtumornecrosisfactoradoesnotaffectinhibitionofdentategranulecellsfollowinginvitroentorhinalcortexlesion
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Scavenging Tumor Necrosis Factor α Does Not Affect Inhibition of Dentate Granule Cells Following In Vitro Entorhinal Cortex Lesion

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