recombinant aav encoding fndc5  (Obio Technology Corp Ltd)

Journal: Journal of Translational Medicine

Article Title: FNDC5/irisin ameliorates diabetes-associated cognitive dysfunction via αVβ5-cAMP signaling to regulate oxidative stress, neuroinflammation and synaptic plasticity

doi: 10.1186/s12967-026-08066-5

Figure Lengend Snippet: Diabetes induces cognitive deficits and decreases hippocampal FNDC5/Irisin expression in rats. ( A , B ) Dynamic changes in body weight and non-fasting blood glucose levels in CON and DM rats over 12 weeks ( n = 12). ( C – E ) Escape latency during MWM training at 4, 8, and 12 weeks ( n = 10 (4w and 8w); n = 12(12w)). ( F ) Average swimming speed during the spatial probe test ( n = 10 (4w and 8w); n = 12(12W)). ( G–I ) probe trial performance: number of platform crossings, latency to first platform crossing, and time spent in the target quadrant ( n = 10 (4w and 8w); n = 12(12W)). ( J ) Representative swimming trajectories on Day 1 and Day 5 of MWM training at different time points. ( K ) Serum Irisin concentrations measured by ELISA at 4, 8, and 12 weeks ( n = 3). ( L , M ) Western blot analysis of hippocampal FNDC5/Irisin expression at 4, 8, and 12 weeks ( n = 3). Data are expressed as mean ± SD. * p < 0.05, ** p < 0.01, *** p < 0.001; ns, not significant

Article Snippet: Recombinant AAV encoding FNDC5 (rAAV2/PHP.eB-Fndc5, pcAAV-CMV-Fndc5-3xFLAG-P2A-EGFP-WPRE, 1.35E + 13 v.g./ml) or control virus (rAAV2/PHP.eB-con, pcAAV-CMV-EGFP-WPRE, 2.40E + 13 v.g./ml) was purchased from OBIO Technology (Shanghai, China).

Techniques: Expressing, Enzyme-linked Immunosorbent Assay, Western Blot

Journal: Journal of Translational Medicine

Article Title: FNDC5/irisin ameliorates diabetes-associated cognitive dysfunction via αVβ5-cAMP signaling to regulate oxidative stress, neuroinflammation and synaptic plasticity

doi: 10.1186/s12967-026-08066-5

Figure Lengend Snippet: Overexpression of FNDC5/irisin ameliorates cognitive decline and hippocampal pathology. ( A ) Representative immunofluorescence image showing hippocampal AAV-FNDC5 injection. ( B – D ) quantification of FNDC5/Irisin protein expression (Western blot), mRNA expression ( n = 3). ( E ) Serum Irisin levels measured by ELISA ( n = 3). ( F ) Representative swimming trajectories in the MWM probe test on Day 1 and Day 5. ( G ) Escape latency during MWM training trials across groups ( n = 12). ( H – K ) Probe trial performance: number of platform crossings, latency to first platform crossing, time spent in the target quadrant and swimming speed ( n = 12). ( L , M ) Representative HE and Nissl staining images of the cortex and hippocampal subregions (CA1, CA3, DG) in different groups. Scale bar: 100 μm. ( N ) Quantification of Nissl-positive neuronal cells in cortex and hippocampal subregions ( n = 3). ( O – Q ) Western blot analysis of APP, phosphorylated Tau (P-Tau), and total Tau expression in hippocampal tissues ( n = 3). Data are expressed as mean ± SD. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001; ns, not significant

Article Snippet: Recombinant AAV encoding FNDC5 (rAAV2/PHP.eB-Fndc5, pcAAV-CMV-Fndc5-3xFLAG-P2A-EGFP-WPRE, 1.35E + 13 v.g./ml) or control virus (rAAV2/PHP.eB-con, pcAAV-CMV-EGFP-WPRE, 2.40E + 13 v.g./ml) was purchased from OBIO Technology (Shanghai, China).

Techniques: Over Expression, Immunofluorescence, Injection, Expressing, Western Blot, Enzyme-linked Immunosorbent Assay, Staining

Journal: Journal of Translational Medicine

Article Title: FNDC5/irisin ameliorates diabetes-associated cognitive dysfunction via αVβ5-cAMP signaling to regulate oxidative stress, neuroinflammation and synaptic plasticity

doi: 10.1186/s12967-026-08066-5

Figure Lengend Snippet: RNA-seq analysis reveals transcriptional regulation by FNDC5/Irisin in hippocampal tissue. ( A ) Volcano plot of differentially expressed genes (DEGs) in the hippocampus of AAV-NC vs. AAV-FNDC5 rats ( n = 6). ( B ) Top 20 enriched KEGG pathways in DEGs ( n = 6). ( C ) The bubble plot of top 30 GO signaling pathways enriched by DEGs ( n = 6)

Article Snippet: Recombinant AAV encoding FNDC5 (rAAV2/PHP.eB-Fndc5, pcAAV-CMV-Fndc5-3xFLAG-P2A-EGFP-WPRE, 1.35E + 13 v.g./ml) or control virus (rAAV2/PHP.eB-con, pcAAV-CMV-EGFP-WPRE, 2.40E + 13 v.g./ml) was purchased from OBIO Technology (Shanghai, China).

Techniques: RNA Sequencing, Protein-Protein interactions

Journal: Journal of Translational Medicine

Article Title: FNDC5/irisin ameliorates diabetes-associated cognitive dysfunction via αVβ5-cAMP signaling to regulate oxidative stress, neuroinflammation and synaptic plasticity

doi: 10.1186/s12967-026-08066-5

Figure Lengend Snippet: Metabolomic profiling reveals the effects of FNDC5/irisin overexpression on hippocampal metabolites in diabetic rats. ( A ) Representative total ion current (TIC) chromatograms of hippocampal metabolites from different groups, showing the overall metabolic fingerprinting ( n = 6). ( B ) QC sample correlation plots, demonstrating the stability and reliability of the metabolomic analysis ( n = 5). ( C ) Principal component analysis (PCA) score plot, illustrating the separation of metabolic profiles among CON, DM, AAV-NC, and AAV-FNDC5 groups ( n = 6). ( D ) Volcano plot of differential metabolites between groups, with red dots representing significantly altered metabolites (|log 2 FC| >1, p < 0.05) ( n = 6). ( E ) Hierarchical clustering heatmap of differential metabolites, showing distinct metabolic patterns across groups. Each row represents a metabolite, and each column represents a sample; colors indicate relative metabolite intensities ( n = 6). ( F ) KEGG pathway enrichment analysis of differential metabolites. Pathways related to cAMP signaling, riboflavin metabolism, citrate cycle (TCA cycle), arginine and proline metabolism, and GABAergic synapse (red boxes) are significantly enriched ( n = 6). ( G – L ) violin plots showing the relative abundances of representative metabolites involved in key pathways, including ( G ) riboflavin, ( H ) phosphatidic acid, ( I ) glutamine, ( J ) citric acid, ( K ) arginine, and ( L ) GABA ( n = 6). ( M ) Differential gene-metabolite co-expression network analysis. Data are presented as mean ± SD; ns: not significant, ** p < 0.001

Article Snippet: Recombinant AAV encoding FNDC5 (rAAV2/PHP.eB-Fndc5, pcAAV-CMV-Fndc5-3xFLAG-P2A-EGFP-WPRE, 1.35E + 13 v.g./ml) or control virus (rAAV2/PHP.eB-con, pcAAV-CMV-EGFP-WPRE, 2.40E + 13 v.g./ml) was purchased from OBIO Technology (Shanghai, China).

Techniques: Metabolomic, Over Expression, Expressing

Journal: Journal of Translational Medicine

Article Title: FNDC5/irisin ameliorates diabetes-associated cognitive dysfunction via αVβ5-cAMP signaling to regulate oxidative stress, neuroinflammation and synaptic plasticity

doi: 10.1186/s12967-026-08066-5

Figure Lengend Snippet: FNDC5/Irisin colocalizes with neurons, microglia, and astrocytes to regulate inflammatory homeostasi. ( A – D ) Representative immunofluorescence images showing the colocalization of Irisin (red) with neuronal marker NeuN (purple), astrocyte marker GFAP (green), and microglial marker Iba1 (yellow) in the ( A ) cortex, ( B ) hippocampal CA3 region, ( C ) hippocampal CA1 region, and ( D ) hippocampal DG region. Nuclei were counterstained with DAPI (blue). ( n = 3, scale bar = 100 μm). ( E – H ) Quantitative analysis of relative fluorescence intensity for Irisin ( E , G ) and NeuN ( F , H ) in cortical ( E , F ) and hippocampal ( G , H ) subregions (CA1, CA3, DG, cortex) ( n = 3). ( I ) FNDC5/Irisin colocalizes with neurons, microglia, and astrocytes ( n = 3). ( J ) Heatmap showing the expression patterns of pro-inflammatory (red) and anti-inflammatory (blue) factors in different groups, as determined by multiplex assay ( n = 3). ( K – R ) Quantitative analysis of pro-inflammatory factors including ( K ) IL-1β, ( L ) IL-6, ( M ) TNF-α, ( N ) KC/GRO, and anti-inflammatory factors including ( O ) IL-4, ( P ) IL-10, ( Q ) IL-13, ( R ) IL-1β/IL-10 ratio in hippocampal tissues ( n = 3). Data are presented as mean ± SD; ns: not significant, p < 0.05, p < 0.01, ** p < 0.001

Article Snippet: Recombinant AAV encoding FNDC5 (rAAV2/PHP.eB-Fndc5, pcAAV-CMV-Fndc5-3xFLAG-P2A-EGFP-WPRE, 1.35E + 13 v.g./ml) or control virus (rAAV2/PHP.eB-con, pcAAV-CMV-EGFP-WPRE, 2.40E + 13 v.g./ml) was purchased from OBIO Technology (Shanghai, China).

Techniques: Immunofluorescence, Marker, Fluorescence, Expressing, Multiplex Assay

Journal: Journal of Translational Medicine

Article Title: FNDC5/irisin ameliorates diabetes-associated cognitive dysfunction via αVβ5-cAMP signaling to regulate oxidative stress, neuroinflammation and synaptic plasticity

doi: 10.1186/s12967-026-08066-5

Figure Lengend Snippet: FNDC5/Irisin overexpression improves dendritic complexity and synaptic plasticity in diabetic rats. ( A ) Representative Golgi staining images showing dendritic morphology in hippocampal CA1, CA3 subregions, and COR across CON, DM, AAV-NC, and AAV-FNDC5 groups. ( B – D ) Sholl analysis quantifying dendritic intersections at different radial distances from the soma for ( B ) total dendrites, ( C ) basal dendrites, and ( D ) apical dendrites. Insets show schematic representations of dendritic arborization patterns ( n = 3). ( E – G ) Quantitative analysis of total dendritic length in ( E ) CA1, ( F ) CA3, and ( G ) CDR regions. ( H ) Representative images of synaptic structures in CA1, CA3, and COR regions visualized by Golgi staining. ( n = 3, scale bar: 10 μm). ( I – K ) Quantitative analysis of synaptic density in ( I ) CA1, ( J ) CA3, and ( K ) COR regions ( n = 3). ( L – N ) Quantitative analysis of dendritic spine subtypes including mushroom spines, stubby spines, and thin spines in hippocampal subregions ( n = 3). ( O ) TEM images showing ultrastructural changes of synapses; Red boxes indicate magnified areas of synaptic regions. Scale bar: 2 μm and 500 nm. ( P – T ) Western blot analysis of BDNF, NGF, PSD-95, and SYN in hippocampal tissues ( n = 3). Data are presented as mean ± SD; ns: not significant, p < 0.05, p < 0.01, ** p < 0.001

Article Snippet: Recombinant AAV encoding FNDC5 (rAAV2/PHP.eB-Fndc5, pcAAV-CMV-Fndc5-3xFLAG-P2A-EGFP-WPRE, 1.35E + 13 v.g./ml) or control virus (rAAV2/PHP.eB-con, pcAAV-CMV-EGFP-WPRE, 2.40E + 13 v.g./ml) was purchased from OBIO Technology (Shanghai, China).

Techniques: Over Expression, Staining, Western Blot

Journal: Journal of Translational Medicine

Article Title: FNDC5/irisin ameliorates diabetes-associated cognitive dysfunction via αVβ5-cAMP signaling to regulate oxidative stress, neuroinflammation and synaptic plasticity

doi: 10.1186/s12967-026-08066-5

Figure Lengend Snippet: FNDC5/Irisin activates the PKA-CREB signaling pathway via the integrin αVβ5 receptor to regulate synaptic plasticity. ( A – C ) Western blot analysis of phosphorylated PKA (P-PKA), total PKA, phosphorylated CREB (P-CREB), and total CREB in hippocampal tissues from CON, DM, AAV-NC, and AAV-FNDC5 groups ( n = 3). ( D – H ) Western blot analysis of P-PKA, total PKA, P-CREB, total CREB, PSD-95, and SYN in SY5Y cells under different treatments ( n = 3). ( I – K ) Western blot analysis of P-PKA, total PKA, P-CREB, and total CREB in SY5Y cells treated with cilengitide trifluoroacetate (avβ5 inhibitor) ( n = 3). Data are presented as mean ± SD; ns: not significant, p < 0.05, p < 0.01, ** p < 0.001, * p < 0.0001

Article Snippet: Recombinant AAV encoding FNDC5 (rAAV2/PHP.eB-Fndc5, pcAAV-CMV-Fndc5-3xFLAG-P2A-EGFP-WPRE, 1.35E + 13 v.g./ml) or control virus (rAAV2/PHP.eB-con, pcAAV-CMV-EGFP-WPRE, 2.40E + 13 v.g./ml) was purchased from OBIO Technology (Shanghai, China).

Techniques: Western Blot