Journal: IBRO Neuroscience Reports

Article Title: Pre-treatment with royal jelly, environmental enrichment, and their combination role in stress induced neurobehavioral deficits in male rats

doi: 10.1016/j.ibneur.2026.03.012

Figure Lengend Snippet: Experimental Timeline: Rats were treated with EE, RJ, and EE + RJ for 14 consecutive days. Stress was induced on days 8–14. Behavioral tests were conducted on days 15–18. On day 19, the animals were decapitated to assess serum corticosterone and hippocampal BDNF levels.

Article Snippet: The evaluation of serum corticosterone levels and hippocampal BDNF levels was conducted using an enzyme-linked immunosorbent assay (ELISA) with a commercially available ELISA kit (E20160505043, Hangzhou Eastbiopharm Co. Ltd., Zhejiang Province, China) and rat BDNF ELISA kits from Boster Biological Technology Co. with a sensitivity limit of 4 pg/ml following the instructions provided by the manufacturer.

Techniques:

Journal: IBRO Neuroscience Reports

Article Title: Pre-treatment with royal jelly, environmental enrichment, and their combination role in stress induced neurobehavioral deficits in male rats

doi: 10.1016/j.ibneur.2026.03.012

Figure Lengend Snippet: The effects of EE and RJ treatment on the hippocampal BDNF expression. The BDNF levels in the stressed group were significantly decreased than in the control group. EE and RJ treatment increased BDNF levels in the stressed rats. *, **, and *** represent p < 0.05, p < 0.01, and p < 0.001 v.s. the Non-stressed control group, respectively; ^^ and ^^^ represent p < 0.01 and p < 0.001 v.s. the Non-treatment stressed group, respectively.

Article Snippet: The evaluation of serum corticosterone levels and hippocampal BDNF levels was conducted using an enzyme-linked immunosorbent assay (ELISA) with a commercially available ELISA kit (E20160505043, Hangzhou Eastbiopharm Co. Ltd., Zhejiang Province, China) and rat BDNF ELISA kits from Boster Biological Technology Co. with a sensitivity limit of 4 pg/ml following the instructions provided by the manufacturer.

Techniques: Expressing, Control

Journal: Cell Reports Medicine

Article Title: BDNF insufficiency exacerbates ALS progression

doi: 10.1016/j.xcrm.2026.102758

Figure Lengend Snippet: Therapeutic benefits of boosting BDNF signal in SOD1 G93A and TDP43 A315T mice with B90-1 (A) Treatment timeline for the SOD1 G93A and TDP43 A315T mice. B90-1 was administered through intravenous injection, and IgG was used as the control. Riluzole was provided per oral with separate vehicle controls. (B and E) Survival curves of SOD1 G93A (B) or TDP43 A315T (E) mice with different treatment. n = 12 mice for each group. Kaplan-Meier analysis was used for statistical comparison. (C and F) Motor function was measured by wire hang test (SOD1 G93A in C and TDP43 A315T in F) at different ages. n = 12 mice for each group to begin with more than 4 mice in each group for the last time point. Data are represented as mean ± SD. Two-way ANOVA with Tukey’s post hoc analysis was used for statistical comparison for the main group effect. (D and G) Quantification of ChAT-positive motor neurons in sections at lumbar L4–6 segments of 16-week-old SOD1 G93A (D) or TDP43 A315T (G) mice with different treatment. n = 3 mice for each group for SOD1 G93A and 6 mice for TDP43 A315T . Data are represented as mean ± SD. Student’s t tests were used for statistical comparisons.

Article Snippet: Bdnf +/−, SOD1G93A and TDP43 were acquired from Jackson Laboratory, Strain #: 002266, 002726 and 010700, respectively.

Techniques: Injection, Control, Comparison

Journal: Frontiers in Cell and Developmental Biology

Article Title: Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression

doi: 10.3389/fcell.2026.1786720

Figure Lengend Snippet: Overview of the cardiac cell composition in cardiomyocyte-BDNF-KO hearts and WT hearts. (A) UMAP reduction plot of the full dataset, which was labeled by unsupervised SNN clustering at a resolution of 0.4. (B) UMAP dimensionality reduction plot of cardiomyocyte-BDNF-KO hearts and WT hearts grouped by sample origin. (C) Dot plot of marker gene expression in cardiac cells. (D) UMAP dimensionality reduction plot after semisupervised cell type annotations. (E) UMAP dimensionality reduction plot of annotated cell types in cardiomyocyte-BDNF-KO hearts and WT hearts grouped by sample origin. (F) Proportions of annotated cardiac cells in cardiomyocyte-BDNF-KO hearts and WT hearts.

Article Snippet: Briefly, BDNF flox/flox mice (Stock #004339, Jackson Laboratory) were crossed with B6.FVB-Tg(Myh6-cre)2182Md/J mice (Stock #011038, Jackson Laboratory) to produce heterozygous Myh6-Cre ± -BDNF flox/+ mice, which were then backcrossed to BDNF flox/flox mice to obtain homozygous Myh6-Cre ± -BDNF flox/flox mice with a mixed background.

Techniques: Labeling, Marker, Gene Expression

Journal: Frontiers in Cell and Developmental Biology

Article Title: Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression

doi: 10.3389/fcell.2026.1786720

Figure Lengend Snippet: DEGs identified in CFs and KEGG and GO enrichment analyses of the DEGs related to cardiac functions and pathways as well as cell‒cell interactions and an analysis the strength of the interactions between cardiomyocyte-BDNF-KO hearts and WT hearts. (A) The number of DEGs (cardiomyocyte-BDNF-KO vs. WT) identified in CFs between cardiomyocyte-BDNF-KO hearts and WT hearts. (B) KEGG and GO enrichment analyses of DEGs related to cardiac functions and pathways of CFs. (C) An analysis of cell–cell interactions in cardiomyocyte-BDNF-KO hearts and WT hearts revealed that the number of cell–cell interactions was significantly increased in cardiomyocyte-BDNF-KO hearts compared with WT hearts. (D) An analysis of cell–cell interactions in cardiomyocyte-BDNF-KO hearts and WT hearts revealed that the strength of cell–cell interactions was significantly increased in cardiomyocyte-BDNF-KO hearts compared with WT hearts.

Article Snippet: Briefly, BDNF flox/flox mice (Stock #004339, Jackson Laboratory) were crossed with B6.FVB-Tg(Myh6-cre)2182Md/J mice (Stock #011038, Jackson Laboratory) to produce heterozygous Myh6-Cre ± -BDNF flox/+ mice, which were then backcrossed to BDNF flox/flox mice to obtain homozygous Myh6-Cre ± -BDNF flox/flox mice with a mixed background.

Techniques:

Journal: Frontiers in Cell and Developmental Biology

Article Title: Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression

doi: 10.3389/fcell.2026.1786720

Figure Lengend Snippet: An analysis of cell‒cell interactions by snRNA-seq revealed that cardiomyocyte-BDNF-KO increases the activity of the TGF-β pathway in cardiac fibroblasts. (A) CellChat cell‒cell interaction analysis revealed that compared with those in WT hearts, the activity of the TGF-β signaling pathway and 67 other signaling pathways in cardiomyocyte-BDNF-KO hearts increased, whereas the activity of 16 signaling pathways in cardiomyocyte-BDNF-KO hearts decreased. In addition, 5 signaling pathways were identified only in the cardiomyocyte-BDNF-KO hearts but not in the WT hearts, whereas 2 signaling pathways were identified only in the WT hearts but not in the cardiomyocyte-BDNF-KO hearts. (B) Analysis of the activity of the TGF-β pathway during interactions between the CFs and other cardiac cells with respect to the function of CFs as ligand-secreting cells in WT hearts and cardiomyocyte-BDNF-KO hearts. (C) Activity of the TGF-β pathway during interactions between the CFs and other cardiac cells with respect to the function of CFs as recipients in WT hearts and cardiomyocyte-BDNF-KO hearts. B–C: Compared with those in WT hearts, the strength of the TGF-β pathway in CFs of cardiomyocyte-BDNF-KO hearts was increased regardless of the type of ligand-secreting cell and recipient cell. (D) snRNA-seq revealed that the expression of key signaling molecules in the TGFβ pathway ( TGF-β1, α-SMA, Col1a1, Col1a2 and Col3a1 ) in CFs of cardiomyocyte-BDNF-KO hearts was significantly higher than that in CFs of WT mice. (E) DEGs identified in the CF snRNA-seq dataset between the cardiomyocyte-BDNF-KO hearts and WT hearts were subjected to a KEGG signaling pathway analysis. Eight genes ( Acvr1, Bmpr2, Dcn, Ep300, Fbn1, Mapk1, Smurf2, and Tgfbr2 ) involved in the TGF-β signaling pathway were enriched, and their expression levels increased.

Article Snippet: Briefly, BDNF flox/flox mice (Stock #004339, Jackson Laboratory) were crossed with B6.FVB-Tg(Myh6-cre)2182Md/J mice (Stock #011038, Jackson Laboratory) to produce heterozygous Myh6-Cre ± -BDNF flox/+ mice, which were then backcrossed to BDNF flox/flox mice to obtain homozygous Myh6-Cre ± -BDNF flox/flox mice with a mixed background.

Techniques: Activity Assay, Protein-Protein interactions, Expressing

Journal: Frontiers in Cell and Developmental Biology

Article Title: Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression

doi: 10.3389/fcell.2026.1786720

Figure Lengend Snippet: CFs express the BDNF receptor TrkB-FL but not BDNF. (A) Anti-Vimentin (marker of CFs) and anti-TrkB (BDNF receptor) double immunofluorescence staining confirmed that the isolated CFs from WT hearts were positive for vimentin and TrkB expression. (B) The results of the qPCR analysis revealed that the CFs did not express BDNF but did express TrkB, BDNF receptor. (C) WB analysis showing that the CFs from WT hearts and CMFs induced by TGF-β treatment expressed the BDNF receptor TrkB but not BDNF. Bend.3: Brain-derived Endothelial cells.3(Bend.3) cell line, used as a positive control for BDNF and TrkB expression. (D) The isolated TrkB bands from the CFs and CMFs used for C-terminal sequencing. (E) The 9-amino acid sequence of the C-terminal sequence of the proteins in “D”. (F) The amino acid sequence of TrkB-FL. The amino acid sequence of the protein in “E” is 100% identical to the C-terminal 9 amino acids of the protein in “F”. (D–F) Protein C-terminal sequencing revealed that CFs express the BDNF full-length receptor TrkB-FL but not the truncated receptor TrkB-T1.

Article Snippet: Briefly, BDNF flox/flox mice (Stock #004339, Jackson Laboratory) were crossed with B6.FVB-Tg(Myh6-cre)2182Md/J mice (Stock #011038, Jackson Laboratory) to produce heterozygous Myh6-Cre ± -BDNF flox/+ mice, which were then backcrossed to BDNF flox/flox mice to obtain homozygous Myh6-Cre ± -BDNF flox/flox mice with a mixed background.

Techniques: Marker, Double Immunofluorescence Staining, Isolation, Expressing, Derivative Assay, Positive Control, Sequencing

Journal: Frontiers in Cell and Developmental Biology

Article Title: Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression

doi: 10.3389/fcell.2026.1786720

Figure Lengend Snippet: The expression levels of key signaling molecules in the TGF-β pathway in the CFs of cardiomyocyte-BDNF-KO hearts are increased, and BDNF and 7,8-DHF treatments decrease the expression of key signaling molecules in the TGF-β pathway in the CFs and CMFs. (A) qPCR analysis revealed that the expression levels of representative key signaling molecules in the TGF-β pathway ( α-SMA (a) , Col1a1 (b) , Col3a1 (c) , and TGF-β (d)) in the CFs of cardiomyocyte-BDNF-KO hearts were significantly higher than those in the WT hearts. *: p < 0.05. n = 3. (B) qPCR analysis revealed that both BDNF treatment and 7,8-DHF treatment decreased the expression levels of key signaling molecules in the TGF-β pathway ( TGF-β, α-SMA, Col1a1 and Col3a1 ) in the CFs of WT hearts in vitro . *: p < 0.05. **: p < 0.01. ***: p < 0.001. n = 3. (C) qPCR analysis showed that both BDNF treatment and 7,8-DHF treatment decreased the expression levels of key signaling molecules in the TGF-β pathway ( TGF-β, α-SMA, Col1a1 and Col3a ) in CMFs in vitro . *: p < 0.05. **: p < 0.01. ***: p < 0.001. n = 3.

Article Snippet: Briefly, BDNF flox/flox mice (Stock #004339, Jackson Laboratory) were crossed with B6.FVB-Tg(Myh6-cre)2182Md/J mice (Stock #011038, Jackson Laboratory) to produce heterozygous Myh6-Cre ± -BDNF flox/+ mice, which were then backcrossed to BDNF flox/flox mice to obtain homozygous Myh6-Cre ± -BDNF flox/flox mice with a mixed background.

Techniques: Expressing, In Vitro

Journal: Frontiers in Cell and Developmental Biology

Article Title: Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression

doi: 10.3389/fcell.2026.1786720

Figure Lengend Snippet: BDNF inhibits the proliferation of CFs and CMFs and promotes the apoptosis of CMFs and the accumulation of CFs and CMFs in S phase but does not induce senescence in CFs or CMFs, and 7,8-DHF has the same effects as BDNF. (A) The results of the CCK8 assay showed that BDNF treatment inhibited the proliferation and survival of CFs and CMFs. n = 4. (B) The results of the CCK-8 assay revealed that 7,8-DHF treatment inhibited the proliferation and survival of CFs and CMFs. n = 4. A and (B) A dose of 100 ng/mL BDNF and 50 μM 7,8-DHF, the BDNF mimic, was suitable for all the following studies in the present study. (C) EdU incorporation combining with flow cytometry assays showed that both BDNF and 7,8-DHF treatment inhibited the proliferation of CFs and CMFs. a: Representative images of flow cytometry analysis using EdU incorporation for proliferation in CFs and CMFs treated with or without BDNF and 7,8-DHF. b: Semiquantitative analysis of the data shown in a. n = 3. (D) The flow cytometry analysis by using Annexin V-AF647/PI double staining revealed that BDNF treatment promoted the apoptosis of CMFs but not of CFs. n = 3. (E) The flow cytometry analysis by using Annexin V-AF647/PI double staining revealed that 7,8-DHF treatment promoted the apoptosis of CMFs and CFs. n = 3. (F) PI staining for the cell cycle and flow cytometry revealed that both BDNF and 7,8-DHF treatments resulted in the accumulation of CFs in S phase. (G) PI staining for the cell cycle and flow cytometry revealed that both BDNF and 7,8-DHF treatments resulted in the accumulation of CMFs in S phase. n = 3. (H) β-Gal staining showed that neither BDNF nor 7,8-DHF treatment increased the number of senescent CFs or CMFs. a: Representative images of CFs treated with BDNF, 7,8-DHF or the control. b: Representative images of CMFs treated with BDNF, 7,8-DHF, or the control. c: Semiquantitative analysis of the data shown in a and b. n = 3. *: p < 0.05. **: p < 0.01. ***: p < 0.001. ****: p < 0.0001.

Article Snippet: Briefly, BDNF flox/flox mice (Stock #004339, Jackson Laboratory) were crossed with B6.FVB-Tg(Myh6-cre)2182Md/J mice (Stock #011038, Jackson Laboratory) to produce heterozygous Myh6-Cre ± -BDNF flox/+ mice, which were then backcrossed to BDNF flox/flox mice to obtain homozygous Myh6-Cre ± -BDNF flox/flox mice with a mixed background.

Techniques: CCK-8 Assay, Flow Cytometry, Double Staining, Staining, Control

Journal: Frontiers in Cell and Developmental Biology

Article Title: Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression

doi: 10.3389/fcell.2026.1786720

Figure Lengend Snippet: BDNF and 7,8-DHF treatments decreased the expression of α-SMA in CFs and CMFs, promoted the phosphorylation of the TrkB receptor in CFs and CMFs, decreased the phosphorylation of Smad2/3, and increased the expression of Samd7 in CMFs. (A) WB analysis revealed that both BDNF treatment and 7,8-DHF treatment decreased the expression of α-SMA, a key protein involved in cardiac fibrosis, in both CFs and CMFs. c: Semiquantitative analysis of the CFs shown in “a”. d: Semiquantitative analysis of the CMFs shown in “b”. (B) WB analysis revealed that both BDNF treatment and 7,8-DHF treatment promoted the phosphorylation of the TrkB receptor in CFs but did not change the expression level of the TrkB receptor; moreover, BDNF treatment and 7,8-DHF treatment did not affect the expression or phosphorylation of Smad2/3 in CFs. b: Semiquantitative analysis of the TrkB receptor levels in CFs shown in “a”. c: Semiquantitative analysis of Smad2/3 levels in CFs shown in “a”. (C) WB analysis revealed that both BDNF treatment and 7,8-DHF treatment promoted the phosphorylation of the TrkB receptor in CMFs, whereas they decreased the phosphorylation of Smad2/3 in CMFs but did not change the expression level of Smad2/3 in CMFs. b: Semiquantitative analysis of the TrkB receptor levels in CMFs shown in “a”. c: Semiquantitative analysis of “Smad2/3 levels in CMFs shown in “a”. (D) qPCR (a) and WB (b and c) analyses confirmed that both BDNF treatment and 7,8-DHF treatment increased the expression level of Smad7 in CMFs. (E) qPCR (a) and WB (b and c) analyses confirmed that neither BDNF nor 7,8-DHF treatment altered the expression level of Smad7 in CFs. *: p < 0.05. **: p < 0.01. ***: p < 0.001. ****: p < 0.0001. n = 3.

Article Snippet: Briefly, BDNF flox/flox mice (Stock #004339, Jackson Laboratory) were crossed with B6.FVB-Tg(Myh6-cre)2182Md/J mice (Stock #011038, Jackson Laboratory) to produce heterozygous Myh6-Cre ± -BDNF flox/+ mice, which were then backcrossed to BDNF flox/flox mice to obtain homozygous Myh6-Cre ± -BDNF flox/flox mice with a mixed background.

Techniques: Expressing, Phospho-proteomics

Journal: Frontiers in Cell and Developmental Biology

Article Title: Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression

doi: 10.3389/fcell.2026.1786720

Figure Lengend Snippet: BDNF-AAV9-mediated ectopic BDNF gene therapy decreased the expression levels of cardiac fibrosis effectors and ameliorated cardiac fibrosis in cardiomyocyte-BDNF-KO hearts in vivo . (A) Masson’s trichrome staining showed that after treatment for 16 weeks in vivo , the fibrotic area of BDNF-AAV9-treated hearts was still larger than that of WT hearts but was significantly smaller than that of NC-AAV9-treated cardiomyocyte-BDNF-KO control hearts. a–c: Cardiomyocyte-BDNF-KO hearts treated with NC-AAV9. d–f: Cardiomyocyte-BDNF-KO hearts treated with BDNF-AAV9. g–i: WT hearts. b and c: Magnified images of a. e–f: Magnified images of d. h–i: Magnified images of g. j: Semiquantitative analysis of fibrosis area (blue) of cardiomyocyte-BDNF-KO hearts treated with NC-AAV9, cardiomyocyte-BDNF-KO hearts treated with BDNF-AAV9 and WT hearts. n = 5. (B) qPCR analysis revealed that compared with those in NC-AAV9-treated cardiomyocyte-BDNF-KO control hearts, BDNF-AAV9 treatment significantly decreased the expression of genes related to TGF-β/Smad2/3-mediated cardiac fibrosis ( TGF-β, α-SMA, Smad3, Cola1, Col3a1 and Fn-1 ) in cardiomyocyte-BDNF-KO hearts. n = 5. *: p < 0.05. **: p < 0.01. ***: p < 0.001. ****: p < 0.0001.

Article Snippet: Briefly, BDNF flox/flox mice (Stock #004339, Jackson Laboratory) were crossed with B6.FVB-Tg(Myh6-cre)2182Md/J mice (Stock #011038, Jackson Laboratory) to produce heterozygous Myh6-Cre ± -BDNF flox/+ mice, which were then backcrossed to BDNF flox/flox mice to obtain homozygous Myh6-Cre ± -BDNF flox/flox mice with a mixed background.

Techniques: Expressing, In Vivo, Staining, Control

Journal: Frontiers in Cell and Developmental Biology

Article Title: Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression

doi: 10.3389/fcell.2026.1786720

Figure Lengend Snippet: BDNF-AAV9-mediated ectopic BDNF gene therapy for cardiomyocyte-BDNF-KO hearts in vivo decreases the activity of the TGF-β/Smad2/3 pathway and increases Smad7 expression. (A) WB analysis revealed that the phosphorylation of the TrkB receptor in BDNF-AAV9-treated hearts was significantly higher than that in NC-AAV9-treated hearts. a: Representative images of WBs. b: Semiquantitative analysis of the data shown in “a”. (B) WB analysis showed that the protein expression levels of TGF-β, Col1, and α-SMA (key effectors of cardiac fibrosis mediated by the TGF-β/Smad2/3 pathway) in BDNF-AAV9-treated cardiomyocyte-BDNF-KO hearts were significantly lower than those in NC-AAV9-treated cardiomyocyte-BDNF-KO hearts. a: Representative images of WBs. b: Semiquantitative analysis of the data shown in “a”. (C) WB analysis showing the levels of phosphorylated Smad2/3 in BDNF-AAV9-treated cardiomyocyte-BDNF-KO hearts and WT hearts were significantly lower than those in NC-AAV9-treated cardiomyocyte-BDNF-KO hearts. a: Representative images of WBs. b: Semiquantitative analysis of the data shown in “a”. (D) WB analysis showed that the Smad7 level in BDNF-AAV9-treated cardiomyocyte-BDNF-KO hearts was significantly higher than that in NC-AAV9-treated cardiomyocyte-BDNF-KO hearts and WT hearts, whereas Smad7 expression in NC-AAV9-treated cardiomyocyte-BDNF-KO hearts was similar to that in WT hearts. a: Representative images of WBs. b: Semiquantitative analysis of the data shown in “a”. n = 3. *: p < 0.05. **: p < 0.01. ***: p < 0.001. ****: p < 0.0001.

Article Snippet: Briefly, BDNF flox/flox mice (Stock #004339, Jackson Laboratory) were crossed with B6.FVB-Tg(Myh6-cre)2182Md/J mice (Stock #011038, Jackson Laboratory) to produce heterozygous Myh6-Cre ± -BDNF flox/+ mice, which were then backcrossed to BDNF flox/flox mice to obtain homozygous Myh6-Cre ± -BDNF flox/flox mice with a mixed background.

Techniques: In Vivo, Activity Assay, Expressing, Phospho-proteomics

Journal: Frontiers in Cell and Developmental Biology

Article Title: Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression

doi: 10.3389/fcell.2026.1786720

Figure Lengend Snippet: Treatment with the BDNF mimic 7,8-DHF attenuates cardiac fibrosis in cardiomyocyte-BDNF-KO hearts in vivo . (A) qPCR revealed that after 7,8-DHF treatment for 6 weeks, the expression of genes related to cardiac fibrosis mediated by the TGF-β/Smad2/3 pathway ( α-SMA, Smad3, and Col3a1 ) was significantly lower in 7,8-DHF-treated cardiomyocyte-BDNF-KO hearts than in untreated cardiomyocyte-BDNF-KO hearts. (B) Masson’s trichrome staining showed that after treatment with 7,8-DHF for 6 weeks in vivo , the fibrotic area of 7,8-DHF-treated cardiomyocyte-BDNF-KO hearts was significantly smaller than that of untreated cardiomyocyte-BDNF-KO hearts, and was larger than to that of WT hearts. a, c and e: Representative images of Masson’s trichrome staining of untreated cardiomyocyte-BDNF-KO hearts, 7,8-DHF-treated cardiomyocyte-BDNF-KO hearts and WT hearts. b: Magnified image of a. d: Magnified image of c. f: Magnified image of e.g: Semiquantitative analysis of the results presented in “a, c and e”. *: p < 0.05. ***: p < 0.001. ****: p < 0.0001. n = 4, 3, 3 (WT, 7,8-DHF treated, and untreated groups).

Article Snippet: Briefly, BDNF flox/flox mice (Stock #004339, Jackson Laboratory) were crossed with B6.FVB-Tg(Myh6-cre)2182Md/J mice (Stock #011038, Jackson Laboratory) to produce heterozygous Myh6-Cre ± -BDNF flox/+ mice, which were then backcrossed to BDNF flox/flox mice to obtain homozygous Myh6-Cre ± -BDNF flox/flox mice with a mixed background.

Techniques: In Vivo, Expressing, Staining

Journal: Frontiers in Cell and Developmental Biology

Article Title: Cardiomyocyte-derived BDNF restricts cardiac fibrosis by decreasing the activity of the TGF-β/Smad2/3 pathway and increasing Smad7 expression

doi: 10.3389/fcell.2026.1786720

Figure Lengend Snippet: Schematic diagram of the molecular mechanism by which cardiomyocyte-derived BDNF and 7,8-DHF inhibit cardiac fibrosis. (A) Cardiomyocyte-derived BDNF acts as an endogenous mediator to restrict cardiac fibrosis by inhibiting CF and CMF proliferation, CF activation and transformation into CMFs and increasing the accumulation of CFs and CMFs in S phase and the apoptosis of CMFs. The BDNF‒TrkB-FL pathway cross-inhibits TGF-β/Smad2/3/α-SMA activity and increases the expression of Smad7. (B) Compared with BDNF, 7,8-DHF can achieve the same effects and modulate the same signaling pathways to ameliorate cardiac fibrosis. This figure was created with BioRender ( https://BioRender.com ).

Article Snippet: Briefly, BDNF flox/flox mice (Stock #004339, Jackson Laboratory) were crossed with B6.FVB-Tg(Myh6-cre)2182Md/J mice (Stock #011038, Jackson Laboratory) to produce heterozygous Myh6-Cre ± -BDNF flox/+ mice, which were then backcrossed to BDNF flox/flox mice to obtain homozygous Myh6-Cre ± -BDNF flox/flox mice with a mixed background.

Techniques: Derivative Assay, Activation Assay, Transformation Assay, Activity Assay, Expressing, Protein-Protein interactions