Regulation of frontal lobe inflammation by aerobic exercise mediated PDE4D in D-gal model rats

Objective: To observe the changes of PDE4D/cAMP/PKA signaling pathway expression and inflammatory response in the frontal lobe of D-gal model rats induced by aerobic exercise and PDE4 inhibitors, and explore whether aerobic exercise regulates the inflammatory response in the frontal lobe of D-gal model rats by regulating the expression of PDE4D, thereby improving the learning and memory ability of rats.Methods 8-week-old rats were randomly divided into 5 groups: control group (group C), D-GAL group (group D), D-Gal exercise group (group DE), D-Gal inhibitor group (group DY) and D-Gal inhibitor exercise group (group DYE). D-gal group was intraperitoneally injected with D-gal, while the control group was intraperitoneally injected with the same dose of normal saline, and the mold was made continuously for 6 weeks. After 6 weeks of D-gal injection, the exercise group underwent aerobic exercise intervention for 8 weeks, and the other groups were fed regularly. 10 days before the end of aerobic exercise training, PDE4 inhibitor was injected intraperitoneally in the inhibitor group, and DMSO solution was injected intraperitoneally in the other groups for 10 days. After the modeling, Morris water maze, immunohistochemistry and Western Blot were used to detect the changes of various indexes in the frontal lobes of rats.Results Before exercise, the escape latency in groups D, DE, DY and DYE was significantly higher than that in group C (P<0.05), and the number of platform crossing times in group C was significantly higher than that in groups D, DE, DY and DYE (P<0.01). There were no significant differences in escape latency and times of platform crossing among groups D, DE, DY and DYE (P>0.05). After exercise, the escape latency of group D was significantly increased compared with group C (P<0.05), while the escape latency of DE, DY and DYE groups was significantly decreased compared with group D (P<0.05), and there was no significant difference among DE, DY and DYE groups (P>0.05). The frequency of crossing the platform of rats in group D was significantly lower than that in group C (P<0.01), while the frequency of crossing the platform of rats in DE, DY and DYE groups was increased compared with that in group D (P<0.01), and there was no significant difference in the frequency of crossing the platform among the three groups of DE, DY and DYE groups (P>0.05). Microglia in group D showed a highly activated state, and the number of activated microglia in group D was significantly higher than that in group C (P<0.05); the number of activated microglia in groups DE, DY and DYE was significantly decreased compared with group D (P<0.05), while there was no significant difference among groups DE, DY and DYE (P>0.05). The expressions of cAMP and PKA in the frontal lobe of rats in group D were the lowest, and the expressions of PDE4D, NF-κB and IL-1β in group D were significantly higher than those in group D (P<0.05), while the expressions of DE, DY and DYE groups were significantly lower than those in group C (P<0.05). There was no significant difference among DE, DY and DYE groups (P>0.05).Conclusions Aerobic exercise can reduce the frontal lobe inflammation of D-gal model rats through the PDE4D/cAMP/PKA signaling pathway, reduce the number of activated microglia and the expression of pro-inflammatory cytokines NF-κB and IL-1β under frontal lobe inflammation, and improve the learning and memory ability of D-gal model rats.