IL-6 mediated degeneration of forebrain GABAergic interneurons and cognitive impairment in aged mice through activation of neuronal NADPH oxidase.

4c ); two-way ANOVA analysis of the genotype×age interaction showed a statistically significant effect for area CA3 (F (1,23) = 23.9, P <0.001) and a strong trend for area CA1 (F (1,23) = 3.1, P = 0.09).

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In addition, as predicted by our results showing that injected IL-6 induces brain Nox2, and that IL-6-/- mice lack induction of Nox2, there was preservation of these interneurons in aged IL-6-/- mice which was highly significant for CA3, and approached significance for CA1.

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We found a substantial and highly significant loss of PV-interneurons in aged hippocampus ( Fig. 4 ), with the CA2-3 region being the most affected (20% decrease for CA1, main effect of age: F (1,17) = 34.4, P <0.05; 45% decrease for CA2-3: main effect of age: F (1,17) = 378.7, P <0.05; 33%, 17% decrease for DG, main effect of age: F (1,17) = 20.1, P <0.05) ( Fig. 5b ), as well as a 17% decrease in prelimbic cortex ( Fig.

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