In addition to forced expression of Fndc5, we attempted to directly save the reduced hippocampal irisin using bilateral intrahippocampal injection of recombinant irisin, which improved hippocampal inflammatory microenvironment of BCAS mice by increasing the level of TGF-β (P = 0.046; Fig. 2I) and IL-10 (P = 0.021; Fig. 2H), as well as the cognitive deficits by enhancing the percentage of freezing time in contextual fear test (P = 0.021; Fig. 2J). Here, TGFB1 is linked to Cognitive impairment.