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 receiving increasing attention.

Methods

Using Cx3cr1^CreERIL-10^-/- transgenic mice and their littermates to study the relationship between TRPC channels and memory impairment.

Results

We demonstrated that Cx3cr1^CreERIL-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 Cx3cr1^CreERIL-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 Cx3cr1^CreERIL-10^-/- mice related to inhibiting NLRP3 inflammasome-associated neuroinflammation.

SUBMITTER: Huo S 

PROVIDER: S-EPMC8620645 | biostudies-literature |

REPOSITORIES: biostudies-literature