Figure 8.

Anti-inflammatory treatment rescued neuronal and behavioral phenotypes of Shn-2 KO mice. Mice were chronically treated with rolipram (Rpm, 4 mg/kg) and ibuprofen (Ib, 400 p.p.m.) for 3 weeks. The treatment significantly decreased GFAP immunoreactivity in the DG of Shn-2 KO mice (a, genotype effect: P<0.0001; genotype × drug interaction: P=0.014; Shn-2^−/−, Veh vs Shn-2^−/−, Rpm+Ib, P=0.0323). There was a tendency of decrease in GFAP expression in the mutant CA1 (b, genotype effect: P<0.0001; genotype × drug interaction: P=0.053; Shn-2^−/−, Veh vs Shn-2^−/−, Rpm+Ib, P=0.051). The treatment did not reverse GFAP expression in the PFC of Shn-2 KO mice (c, genotype effect: P=0.0717; genotype × drug interaction: P=0.3662). The reductions of parvalbumin in CA1 (d, genotype effect: P<0.0001) or PFC (e, genotype effect: P=0.0002) were not rescued by the treatment. Increased expression of doublecortin (f, genotype effect: P=0.0014; genotype × drug interaction: P=0.0014; Shn-2^−/−, Veh vs Shn-2^−/−, Rpm+Ib, P=0.0109) and calretinin (g, genotype effect: P<0.0001; genotype × drug interaction: P=0.0019; Shn-2^−/−, Veh vs Shn-2^−/−, Rpm+Ib, P=0.0028) in the DG of Shn-2 KO mice were attenuated by the treatment, while decreased expressions of calbindin (h, genotype effect: P<0.0001) or GAD67 (i, genotype effect: P<0.0001) in the mutant DG were not rescued by the treatment. Working memory (j, genotype effect: P<0.0001; genotype × drug interaction: P=0.0504; Shn-2^−/−, Veh vs Shn-2^−/−, Rpm+Ib, P=0.0042) and nest-building behavior (k, genotype effect: P<0.0001; genotype × drug interaction: P=0.1542; Shn-2^−/−, Veh vs Shn-2^−/−, Rpm+Ib, P=0.0407) were significantly improved by the anti-inflammatory treatment in Shn-2 KO mice. On the other hand, hyperlocomotor activity (l), impaired PPI (m), or anhedonia in the sucrose preference test (n, genotype effect: P=0.006) were not improved. n=5–10 per group. Rpm, rolipram; Ib, ibuprofen; ns, not significant; *P<0.05, **P<0.01.