Upregulation of TRPC5 in hippocampal excitatory synapses improves memory impairment associated with neuroinflammation in microglia knockout IL-10 mice

Abstract Background Members of the transient receptor potential canonical (TRPC) protein family are widely distributed in the hippocampus of mammals and exert respective and cooperative influences on the functions of neurons. The relationship between specific TRPC subtypes and neuroinflammation is r...

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Autores principales:	Shiji Huo, Jiling Ren, Yunqing Ma, Ahsawle Ozathaley, Wenjian Yuan, Hong Ni, Dong Li, Zhaowei Liu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	IL-10 Microglia TRPC5 NLRP3 Memory Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/3a2698c7b5324d8e826c504e5844af29
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spelling	oai:doaj.org-article:3a2698c7b5324d8e826c504e5844af292021-11-28T12:37:39ZUpregulation of TRPC5 in hippocampal excitatory synapses improves memory impairment associated with neuroinflammation in microglia knockout IL-10 mice10.1186/s12974-021-02321-w1742-2094https://doaj.org/article/3a2698c7b5324d8e826c504e5844af292021-11-01T00:00:00Zhttps://doi.org/10.1186/s12974-021-02321-whttps://doaj.org/toc/1742-2094Abstract Background Members of the transient receptor potential canonical (TRPC) protein family are widely distributed in the hippocampus of mammals and exert respective and cooperative influences on the functions of neurons. The relationship between specific TRPC subtypes and neuroinflammation is receiving increasing attention. Methods Using Cx3cr1CreERIL-10−/− transgenic mice and their littermates to study the relationship between TRPC channels and memory impairment. Results We demonstrated that Cx3cr1CreERIL-10−/− mice displayed spatial memory deficits in object location recognition (OLR) and Morris water maze (MWM) tasks. The decreased levels of TRPC4 and TRPC5 in the hippocampal regions were verified via reverse transcription polymerase chain reaction, western blotting, and immunofluorescence tests. The expression of postsynaptic density protein 95 (PSD95) and synaptophysin in the hippocampus decreased with an imbalance in the local inflammatory environment in the hippocampus. The number of cells positive for ionized calcium-binding adaptor molecule 1 (Iba1), a glial fibrillary acidic protein (GFAP), increased with the high expression of interleukin 6 (IL-6) in Cx3cr1CreERIL-10−/− mice. The nod-like receptor protein 3 (NLRP3) inflammasome was also involved in this process, and the cytokines IL-1β and IL-18 activated by NLRP3 were also elevated by western blotting. The co-localization of TRPC5 and calmodulin-dependent protein kinase IIα (CaMKIIα) significantly decreased TRPC5 expression in excitatory neurons. AAV9-CaMKIIα-TRPC5 was used to upregulate TRPC5 in excitatory neurons in the hippocampus. Conclusions The results showed that the upregulation of TRPC5 improved the memory performance of Cx3cr1CreERIL-10−/− mice related to inhibiting NLRP3 inflammasome-associated neuroinflammation. Graphical AbstractShiji HuoJiling RenYunqing MaAhsawle OzathaleyWenjian YuanHong NiDong LiZhaowei LiuBMCarticleIL-10MicrogliaTRPC5NLRP3MemoryNeurology. Diseases of the nervous systemRC346-429ENJournal of Neuroinflammation, Vol 18, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	IL-10 Microglia TRPC5 NLRP3 Memory Neurology. Diseases of the nervous system RC346-429
spellingShingle	IL-10 Microglia TRPC5 NLRP3 Memory Neurology. Diseases of the nervous system RC346-429 Shiji Huo Jiling Ren Yunqing Ma Ahsawle Ozathaley Wenjian Yuan Hong Ni Dong Li Zhaowei Liu Upregulation of TRPC5 in hippocampal excitatory synapses improves memory impairment associated with neuroinflammation in microglia knockout IL-10 mice
description	Abstract Background Members of the transient receptor potential canonical (TRPC) protein family are widely distributed in the hippocampus of mammals and exert respective and cooperative influences on the functions of neurons. The relationship between specific TRPC subtypes and neuroinflammation is receiving increasing attention. Methods Using Cx3cr1CreERIL-10−/− transgenic mice and their littermates to study the relationship between TRPC channels and memory impairment. Results We demonstrated that Cx3cr1CreERIL-10−/− mice displayed spatial memory deficits in object location recognition (OLR) and Morris water maze (MWM) tasks. The decreased levels of TRPC4 and TRPC5 in the hippocampal regions were verified via reverse transcription polymerase chain reaction, western blotting, and immunofluorescence tests. The expression of postsynaptic density protein 95 (PSD95) and synaptophysin in the hippocampus decreased with an imbalance in the local inflammatory environment in the hippocampus. The number of cells positive for ionized calcium-binding adaptor molecule 1 (Iba1), a glial fibrillary acidic protein (GFAP), increased with the high expression of interleukin 6 (IL-6) in Cx3cr1CreERIL-10−/− mice. The nod-like receptor protein 3 (NLRP3) inflammasome was also involved in this process, and the cytokines IL-1β and IL-18 activated by NLRP3 were also elevated by western blotting. The co-localization of TRPC5 and calmodulin-dependent protein kinase IIα (CaMKIIα) significantly decreased TRPC5 expression in excitatory neurons. AAV9-CaMKIIα-TRPC5 was used to upregulate TRPC5 in excitatory neurons in the hippocampus. Conclusions The results showed that the upregulation of TRPC5 improved the memory performance of Cx3cr1CreERIL-10−/− mice related to inhibiting NLRP3 inflammasome-associated neuroinflammation. Graphical Abstract
format	article
author	Shiji Huo Jiling Ren Yunqing Ma Ahsawle Ozathaley Wenjian Yuan Hong Ni Dong Li Zhaowei Liu
author_facet	Shiji Huo Jiling Ren Yunqing Ma Ahsawle Ozathaley Wenjian Yuan Hong Ni Dong Li Zhaowei Liu
author_sort	Shiji Huo
title	Upregulation of TRPC5 in hippocampal excitatory synapses improves memory impairment associated with neuroinflammation in microglia knockout IL-10 mice
title_short	Upregulation of TRPC5 in hippocampal excitatory synapses improves memory impairment associated with neuroinflammation in microglia knockout IL-10 mice
title_full	Upregulation of TRPC5 in hippocampal excitatory synapses improves memory impairment associated with neuroinflammation in microglia knockout IL-10 mice
title_fullStr	Upregulation of TRPC5 in hippocampal excitatory synapses improves memory impairment associated with neuroinflammation in microglia knockout IL-10 mice
title_full_unstemmed	Upregulation of TRPC5 in hippocampal excitatory synapses improves memory impairment associated with neuroinflammation in microglia knockout IL-10 mice
title_sort	upregulation of trpc5 in hippocampal excitatory synapses improves memory impairment associated with neuroinflammation in microglia knockout il-10 mice
publisher	BMC
publishDate	2021
url	https://doaj.org/article/3a2698c7b5324d8e826c504e5844af29
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Upregulation of TRPC5 in hippocampal excitatory synapses improves memory impairment associated with neuroinflammation in microglia knockout IL-10 mice

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