Loss of insulin signaling in astrocytes exacerbates Alzheimer-like phenotypes in a 5xFAD mouse model.

Insulin-stimulated phosphorylation of IR/IGF1R in the cortex following peripheral insulin injection also tended to be decreased in the iGIRKO mice compared to control, but this did not reach statistical significance in the iGIRKO/5xFAD group in this bulk tissue analysis ( SI Appendix , Fig.

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Likewise, when mice were returned to the chambers on the next day but without foot shock (context test), again both iGIRKO and 5xFAD showed a trend toward increased percentage of freezing time compared to the IR f/f control mice, and this increase became significant in the iGIRKO/5xFAD mice, indicating additivity between the 5xFAD effect and loss of astrocytic IR signaling (IR f/f vs iGIRKO/5xFAD, P < 0.001, Fig. 2 H ).

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