NL1 expression level in Nrx1β and the excitability of PV interneurons in mice with POCD

Effects of NL1 on the expression level of neurexin-1β (Nrx1β) and the excitability of parvalbumin (PV) interneurons in mice with postoperative cognitive dysfunction (POCD) were explored. Eighty 10-month-old C57BL/6 male mice were randomly divided into four groups: control group, control+empty vector group (Control+EV), anesthesia surgery+empty vector group (POCD+EV group) and anesthesia+NL1 overexpression group (POCD+NL1 group), (n=20 per group). The behavioral differences of mice in the four groups were analyzed by means of open field test and fear conditioning test. The expression levels of NL1, PV and Nrx1β were detected by western blot analysis, and the binding between NL1 and Nrx1β was determined by co-immunoprecipitation. The expression level of postsynaptic density protein 95 (PSD95) in hippocampus and changes in the excitability of PV interneurons were further detected. Control and Control+EV groups had no significant difference in each index (P>0.05). Compared with Control+EV group, the percentage of cued freezing time in POCD+EV group decreased significantly, while percentage of cued freezing time was significantly increased in POCD+NL1 group and POCD+EV group (P<0.01). The differences in freezing time were not statistically significant among the 4 groups in the tone-related fear test (P>0.05). Then NL1 was overexpressed in mice with POCD, the protein levels of PV, Nrx1β and PSD95 were subsequently increased, and the interaction between NL1 and Nrx1β protein was enhanced, dramatically increasing the excitability of PV interneurons. The overexpression of NL1 can upregulate the expression levels of PV, Nrx1β and PSD95 in mice with POCD, enhance the interaction between NL1 and Nrx1β and further increase the excitability of PV interneurons, thus restoring the hippocampus-dependent memorial and cognitive impairment in POCD.