Journal: Brain, behavior, and immunity
Article Title: Irisin reprograms microglia through activation of STAT6 and prevents cognitive dysfunction after surgery in mice.
doi: 10.1016/j.bbi.2024.12.019
Figure Lengend Snippet: Fig. 9. Schematic representation of the mechanism of irisin in preventing cognitive dysfunction induced by LPS or surgery. ①Exogenous irisin crosses the blood–brain barrier (BBB). ②Irisin directly targets the αVβ5 integrin receptor in microglia and further inhibits the expression of β5 integrin. ③The nuclear transcription factor STAT6 is further activated to promote the polarization of microglia toward the M2 anti-inflammatory phenotype. STAT, signal transducer and activator of transcription. ④Simultaneously, STAT6 inhibits NF-κB activation, and inhibits the polarization to the M1 proinflammatory phenotype induced by LPS or surgery. NF-κB, nuclear factor kappa-B. ⑤Irisin treatment leads to increased expression of anti-inflammatory mediators (namely, IL-10 and Arg-1) and BDNF, and inhibited the expression of proinflammatory factors (namely, IL-1β, IL-18, and TNF-α), thus improving the immune microenvironment. IL, interleukin; Arg-1, arginase-1; BDNF, brain-derived neurotrophic factor. TNF, tumor necrosis factor. ⑥Irisin maintains neuronal homeostasis (including number, dendritic spine density, excitability). ⑦Irisin effectively prevents neurocognitive dysfunction in LPS-induced adult neuroinflammatory mice and surgery/anesthesia-induced early cognitive dysfunction aged mice.
Article Snippet: For staining, the dHPC brain slices were washed 3 times with phosphatebuffered saline (PBS) for 5 min, blocked with a buffer containing 5 % bull serum albumin and 0.3 % Triton X-100 for 1 h, incubated with primary antibodies (1:500), including FNDC5/irisin (ab13190, Abcam), Irisin (H-067–17, Phoenix Pharmaceuticals), Iba1 (ab5076, Abcam), Integrin β5 (3629S, CST), Phospho-NF-κB p65 (3033 T, CST), NF-κB p65 (8242S, CST), STAT6 (5397; CST), Phospho-STAT6 (Tyr641) (56554; CST), c-Fos (2250 s, CST), and NeuN (ab104224, Abcam) at 4 ◦C overnight.
Techniques: Expressing, Activation Assay, Derivative Assay