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Novel role of NCoR1 in impairing spatial memory through the mediation of a novel interacting protein DEC2
Ist Teil von
Cellular and molecular life sciences : CMLS, 2024-12, Vol.81 (1), p.273, Article 273
Ort / Verlag
Cham: Springer International Publishing
Erscheinungsjahr
2024
Quelle
SpringerLink Journals
Beschreibungen/Notizen
Long-term memory formation requires de novo RNA and protein synthesis. Using differential display PCR, we found that the
NCoR1
cDNA fragment is differentially expressed between fast learners and slow learners, with fast learners showing a lower expression level than slow learners in the water maze learning task. Fast learners also show lower
NCoR1
mRNA and protein expression levels. In addition, spatial training decreases both
NCoR1
mRNA and protein expression, whereas
NCoR1
conditional knockout (cKO) mice show enhanced spatial memory. In studying the molecular mechanism, we found that spatial training decreases the association between NCoR1 and DEC2. Both NCoR1 and DEC2 suppress the expression of BDNF, integrin α3 and SGK1 through C/EBPα binding to their DNA promoters, but overexpression of DEC2 in
NCoR1
cKO mice rescues the decreased expression of these proteins compared with
NCoR1 loxP
mice overexpressing DEC2. Further, spatial training decreases DEC2 expression. Spatial training also enhances C/EBPα binding to
Bdnf
,
Itga3
and
Sgk1
promoters, an effect also observed in fast learners, and both NCoR1 and DEC2 control C/EBPα activity. Whereas knockdown of BDNF, integrin α3 or SGK1 expression impairs spatial learning and memory, it does not affect Y-maze performance, suggesting that BDNF, integrin α3 and SGK1 are involved in long-term memory formation, but not short-term memory formation. Moreover, NCoR1 expression is regulated by the JNK/c-Jun signaling pathway. Collectively, our findings identify DEC2 as a novel interacting protein of NCoR1 and elucidate the novel roles and mechanisms of NCoR1 and DEC2 in negative regulation of spatial memory formation.