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Sirt6 regulated the microglial activation and the depression behavior through Nrf2-HO1 signaling in vivo (A) Experimental timeline of tamoxifen administration, AAV9-Cx3cr1-Nrf2 injection, LPS challenge, and behavioral tests in Sirt6 MCKO mice. (B) Western blot analysis of NRF2 levels after AAV9-Cx3cr1-Nrf2 injection. n = 3 mice. (C-D) Immobility time in TST (C) and FST (D). n = 8 mice. (E) TAC, MDA, SOD, and GSH/GSSG levels at 5 days after LPS injection. n = 4 mice. (F-L) Immunostaining of GFAP and IBA1 in the hippocampus area at 5 days after LPS injection (F); Quantification of (G) IBA1 + and (H) GFAP + cell counts, along with microglial morphology parameters: (I) number of branches, (J) average branch length, (K) total branch length, and (L) soma area. n = 4 mice. (M) qPCR analysis of TNF-α,IL-6, and IL-1β mRNA levels in the microglial sorted from the hippocampus brain tissue. n = 4 mice. (N) Western blot analysis of NRF2 downstream signaling component protein levels in microglia sorted from the hippocampus. n = 4 mice. Data are mean ± SEM. Statistical significance between two groups was determined by an unpaired two-tailed Student's t-test.

Journal: Neurobiology of Stress

Article Title: Microglial SIRT6 confers protection against neuroinflammation-associated depression through NRF2-HO1 signaling

doi: 10.1016/j.ynstr.2026.100804

Figure Lengend Snippet: Sirt6 regulated the microglial activation and the depression behavior through Nrf2-HO1 signaling in vivo (A) Experimental timeline of tamoxifen administration, AAV9-Cx3cr1-Nrf2 injection, LPS challenge, and behavioral tests in Sirt6 MCKO mice. (B) Western blot analysis of NRF2 levels after AAV9-Cx3cr1-Nrf2 injection. n = 3 mice. (C-D) Immobility time in TST (C) and FST (D). n = 8 mice. (E) TAC, MDA, SOD, and GSH/GSSG levels at 5 days after LPS injection. n = 4 mice. (F-L) Immunostaining of GFAP and IBA1 in the hippocampus area at 5 days after LPS injection (F); Quantification of (G) IBA1 + and (H) GFAP + cell counts, along with microglial morphology parameters: (I) number of branches, (J) average branch length, (K) total branch length, and (L) soma area. n = 4 mice. (M) qPCR analysis of TNF-α,IL-6, and IL-1β mRNA levels in the microglial sorted from the hippocampus brain tissue. n = 4 mice. (N) Western blot analysis of NRF2 downstream signaling component protein levels in microglia sorted from the hippocampus. n = 4 mice. Data are mean ± SEM. Statistical significance between two groups was determined by an unpaired two-tailed Student's t-test.

Article Snippet: Sirt6 flox/flox ( Sirt6 fl/fl )mice (Stock NM-CKO-200241) were provided by Shanghai Model Organisms, Nrf2 flox/flox ( Nrf2 fl/fl ) mice (Stock 025433) and Cx3cr1 -CreERT2 mice (Stock 021160) were obtained from the Jackson Laboratory.

Techniques: Activation Assay, In Vivo, Injection, Western Blot, Immunostaining, Two Tailed Test

Overexpression of Sirt6 in microglial improved the depression behavior and impeded the microglial activation (A) Experimental timeline depicting tamoxifen administration, followed by tail vein injection of AAV9-Cx3cr1-Sirt6, subsequent LPS challenge, and finally, a series of behavioral tests. (B) Western blot analysis of SIRT6 expression after AAV9-Cx3cr1-Sirt6 injection. n = 3 mice. (C-D) The immobility time was quantified in TST (C) and FST (D). n = 8 mice. (E) TAC, MDA, SOD, and GSH/GSSG levels at 5 days after LPS injection. (F-L) Immunostaining of GFAP and IBA1 in the hippocampus area at 5 days after LPS injection (F); Quantification of (G) IBA1 + and (H) GFAP + cell counts, along with microglial morphology parameters: (I) number of branches, (J) average branch length, (K) total branch length, and (L) soma area. n = 4 mice.(M) qPCR analysis of TNF-α,IL-6, and IL-1β mRNA levels in the microglial sorted from the hippocampus brain tissue. n = 4 mice. Data are mean ± SEM. Statistical significance between two groups was determined by an unpaired two-tailed Student's t-test.

Journal: Neurobiology of Stress

Article Title: Microglial SIRT6 confers protection against neuroinflammation-associated depression through NRF2-HO1 signaling

doi: 10.1016/j.ynstr.2026.100804

Figure Lengend Snippet: Overexpression of Sirt6 in microglial improved the depression behavior and impeded the microglial activation (A) Experimental timeline depicting tamoxifen administration, followed by tail vein injection of AAV9-Cx3cr1-Sirt6, subsequent LPS challenge, and finally, a series of behavioral tests. (B) Western blot analysis of SIRT6 expression after AAV9-Cx3cr1-Sirt6 injection. n = 3 mice. (C-D) The immobility time was quantified in TST (C) and FST (D). n = 8 mice. (E) TAC, MDA, SOD, and GSH/GSSG levels at 5 days after LPS injection. (F-L) Immunostaining of GFAP and IBA1 in the hippocampus area at 5 days after LPS injection (F); Quantification of (G) IBA1 + and (H) GFAP + cell counts, along with microglial morphology parameters: (I) number of branches, (J) average branch length, (K) total branch length, and (L) soma area. n = 4 mice.(M) qPCR analysis of TNF-α,IL-6, and IL-1β mRNA levels in the microglial sorted from the hippocampus brain tissue. n = 4 mice. Data are mean ± SEM. Statistical significance between two groups was determined by an unpaired two-tailed Student's t-test.

Article Snippet: Sirt6 flox/flox ( Sirt6 fl/fl )mice (Stock NM-CKO-200241) were provided by Shanghai Model Organisms, Nrf2 flox/flox ( Nrf2 fl/fl ) mice (Stock 025433) and Cx3cr1 -CreERT2 mice (Stock 021160) were obtained from the Jackson Laboratory.

Techniques: Over Expression, Activation Assay, Injection, Western Blot, Expressing, Immunostaining, Two Tailed Test