Abstract
BackgroundMembers 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.MethodsUsing Cx3cr1CreERIL-10−/− transgenic mice and their littermates to study the relationship between TRPC channels and memory impairment.ResultsWe 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.ConclusionsThe results showed that the upregulation of TRPC5 improved the memory performance of Cx3cr1CreERIL-10−/− mice related to inhibiting NLRP3 inflammasome-associated neuroinflammation.Graphical
Highlights
Introduction Thetransient receptor potential canonical (TRPC) protein family has seven members (TRPC1 to TRPC7) that form homo- and/or heteromorphic tetramers
We focused on the effects of IL-10 induced from microglial cells on animal cognitive and behavioral abilities to explore the role of TRPC and nod-like receptor protein 3 (NLRP3) in the hippocampus during this process
Inhibition of the GABAergic system has memoryfacilitating effects, whereas stimulation produces memory impairment. These results suggest that the effect of TRPC4 or 5 downregulation on learning and memory in Cx3cr1CreERIL-10−/− mice mainly acted on excitatory neurons
Summary
Introduction TheTRPC protein family has seven members (TRPC1 to TRPC7) that form homo- and/or heteromorphic tetramers. Evidence is converging to show the involvement of TRPC channels in cognitive functions, since multiple TRPC subtypes are highly expressed in the hippocampus. The function of the TRPC1/4/5 subfamily plays a key role in spatial working memory formation [3], since TRPC1/4/5−/− mice exhibited deficiencies in adapting to a new challenge in a relearning task. 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. Methods: Using Cx3cr1CreERIL-10−/− transgenic mice and their littermates to study the relationship between TRPC channels and memory impairment. 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
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