Isoflurane triggers the acute cognitive impairment of aged rats by damaging hippocampal neurons via the NR2B/CaMKII/CREB pathway.

Isoflurane was responsible for acute neuronal impairment, but its potential molecular mechanisms in damaging hippocampal neurons had not been clearly understood. This study aimed to explore the underlying mechanism of how isoflurane affected the cognitive function of aged rats by damaging the hippocampal neurons. Acute cognitive impairment was found in aged Wistar rats via Morris water maze test and Y-maze test after isoflurane anesthesia in a dose-dependent manner compared with the control group in vivo. Isoflurane also decreased the viabilities and strengthened the apoptotic potential of hippocampal neurons by damaging the mitochondria in a time-dependent manner compared with the control group which was reported by MTT, immunofluorescent assay, flow cytometry and western blot assay in vitro. Isoflurane jeopardized hippocampal neurons by directly inactivating the NR2B/CaMKII/CREB pathway and its harmful effects could be ameliorated by adding CaMKII activator CdCl2. These findings provided evidence that the cognitive ability of aged rats was injured by isoflurane exposure and isoflurane also inhibited the viability and enhanced the apoptosis of hippocampal neurons by damaging the mitochondria through inhibition of the NR2B/CaMKII/CREB pathway and its harmful roles could be partially ameliorated by CdCl2. Our study demonstrated that isoflurane could cause acute neuronal damage and we provided fresh insights that contributed to the safe use of anesthetic agents and the prevention of PND in elderly people.

ID1 inhibits foot-and-mouth disease virus replication via targeting of interferon pathways.

Inhibitor of DNA-binding 1 (ID1) protein has been studied intensively for its functions in tumorigenesis and maintenance of stem cell-like properties, but its roles in virus infection are less understood. In the present study, we have clearly shown that the foot-and-mouth disease virus (FMDV) promotes ID1 degradation via Cdh1-mediated ubiquitination to facilitate its replication. Mechanistic investigations reveal Forkhead Box O1 (FOXO1) as an ID1 partner, which suppresses interferon regulatory factors 3 expression and interferon (IFN) production. Further investigation identified that ID1 suppresses FOXO1 transcription activity through HDAC4-mediated deacetylation, promoting IFN production and antiviral immune response. These studies establish a prominent role for ID1 in suppressing FDMV replication, which may be extended to other viruses.