trem2 inhibitor trem2  (MedChemExpress)

Journal: Frontiers in Immunology

Article Title: Trem2 activation by renal tubular debris sustains Arg1 + macrophage survival and promotes tubular epithelial repair in renal ischemia–reperfusion injury

doi: 10.3389/fimmu.2026.1819941

Figure Lengend Snippet: Trem2, Msr1, and Spp1 are co-upregulated in Arg1hiEcm1hi ECM-Remodeling Macrophages following IRI and in human AKI kidneys. (A) Differential expression analysis of monocyte/macrophage subsets across multiple time points after IRI reveals marked temporal heterogeneity in gene expression profiles. (B) Trem2 and Spp1 display sustained upregulation during both the early (days 1–3) and intermediate-to-late (days 4–11) phases post-IRI, whereas Msr1 expression is not significantly elevated at day 11. (C) FeaturePlot analysis shows that Trem2, Msr1 , and Spp1 are predominantly expressed in Arg1hiEcm1hi ECM-Remodeling Mac (Cluster 1). (D) Dimensionality reduction and clustering of a publicly available human kidney single-cell RNA-seq dataset identify five major populations: distal tubule & collecting duct (DT&CD), endothelial cells (Endo), monocytes/macrophages (Mono/Mac), proximal tubules (PT), and T/NK cells. (E) Canonical marker gene expression delineates each cluster. (F) Within the monocyte/macrophage population, TREM2, MSR1 , and SPP1 are markedly upregulated in AKI kidneys, whereas APOE remains unchanged. (G) TREM2 and MSR1 are specifically restricted to the monocyte/macrophage compartment, while SPP1 and APOE are also induced in renal tubular epithelial and other immune cells following AKI. (H) KPMP database analysis of Western individuals (28 healthy controls, 14 AKI). (I, J) Transcriptional levels of TREM2, APOE, SPP1 , and MSR1 in monocyte/macrophage subsets. TREM2 is enriched in M2 macrophages and upregulated in AKI alongside APOE and SPP1 , with MSR1 unchanged.

Article Snippet: In the renal tubular cell debris–stimulated group, the TREM2 inhibitor TREM2-IN-1 (HY-160421, MedChemExpress) was added at a concentration of 5 μM to assess cell proliferative activity and apoptosis.

Techniques: Quantitative Proteomics, Gene Expression, Expressing, Single Cell, RNA Sequencing, Marker, Western Blot

Journal: Frontiers in Immunology

Article Title: Trem2 activation by renal tubular debris sustains Arg1 + macrophage survival and promotes tubular epithelial repair in renal ischemia–reperfusion injury

doi: 10.3389/fimmu.2026.1819941

Figure Lengend Snippet: Trem2 and Apoe coordinate lipid metabolic pathways in Arg1 hi Ecm1 hi ECM-Remodeling Macrophages after IRI. (A) Trajectory analysis positions Arg1 hi Ecm1 hi ECM-Remodeling Mac (Cluster 1) and Nusap1 hi Birc5 hi Proliferative Mac (Cluster 6) at terminal branches, indicating terminal differentiation states. (B, C) K-means clustering of pseudotime-dependent genes identifies four dynamic modules. Module 1 is enriched in late-stage lymphocyte activation and tissue remodeling, Module 2 in intermediate lipid metabolism (including lipid localization and transport), Module 3 in early injury responses (hematopoiesis, regeneration, chemotaxis), and Module 4 in adhesion and inflammatory regulation. Trem2 , Arg1 , Spp1 , Msr1 , Apoe , and Lpl cluster within Module 2. (D) Trem2 , Msr1 , Lpl , Spp1 , and Apoe participate in lipid-related pathways. (E) Gene co-expression networks reveal Trem2 , Apoe , and Spp1 co-expressed with Arg1 in Arg1 hi Ecm1 hi ECM-Remodeling Mac.

Article Snippet: In the renal tubular cell debris–stimulated group, the TREM2 inhibitor TREM2-IN-1 (HY-160421, MedChemExpress) was added at a concentration of 5 μM to assess cell proliferative activity and apoptosis.

Techniques: Activation Assay, Chemotaxis Assay, Expressing

Journal: Frontiers in Immunology

Article Title: Trem2 activation by renal tubular debris sustains Arg1 + macrophage survival and promotes tubular epithelial repair in renal ischemia–reperfusion injury

doi: 10.3389/fimmu.2026.1819941

Figure Lengend Snippet: Trem2 is co-expressed with Arg1 in renal macrophages during early IRI, and its inhibition exacerbates acute kidney injury. (A) Dynamic expression profiles of Arg1 , Trem2 , Spp1 , and Apoe mRNA levels in kidney tissues at various time points post-IRI ( n = 8-9). (B, C) Multiplex immunofluorescence staining and quantitative analysis illustrating the spatial distribution and infiltration of Trem2 + , Arg1 + , and F4/80 + cells in sham-operated kidneys and at 1, 3, 7, and 14 days post-IRI ( n = 4). (D) Schematic illustration of the experimental protocol: mice received intraperitoneal injections of the Trem2 inhibitor (TREM2-IN-1) prior to IRI induction. (E, F) Immunofluorescence analysis and quantification demonstrating a significant downregulation of Trem2 protein expression in the TREM2-IN-1–treated group compared to the control group at days 1 and 3 post-IRI ( n = 4). (G) Histopathological evaluation of the kidney showing that pharmacological inhibition of Trem2 significantly aggravates tubular epithelial injury following IRI. (H) Kidney function assessment (serum BUN and Scr levels) confirming that TREM2-IN-1 treatment further worsens renal impairment during the early phase of IRI (days 1 and 3) ( n = 4). Significance was evaluated using Student’s unpaired t test and one-way ANOVA followed by Tukey’s test. Tubular injury score were analyzed using the Kruskal–Wallis test followed by Dunn’s multiple comparisons test. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001, ns , no significance.

Article Snippet: In the renal tubular cell debris–stimulated group, the TREM2 inhibitor TREM2-IN-1 (HY-160421, MedChemExpress) was added at a concentration of 5 μM to assess cell proliferative activity and apoptosis.

Techniques: Inhibition, Expressing, Multiplex Assay, Immunofluorescence, Staining, Control

Journal: Frontiers in Immunology

Article Title: Trem2 activation by renal tubular debris sustains Arg1 + macrophage survival and promotes tubular epithelial repair in renal ischemia–reperfusion injury

doi: 10.3389/fimmu.2026.1819941

Figure Lengend Snippet: Tubular cell debris triggers Trem2 upregulation and stimulates proliferation in Arg1 + macrophages. (A, B) IL-4 treatment of RAW264.7 cells for 24 h significantly increased Arg1 transcription, Arg1 + macrophage proportion, and intracellular Arg1 protein intensity ( n = 3-6). (C, D) To mimic the IRI microenvironment, freeze-thaw–induced tubular cell debris were co-cultured with IL-4–pretreated RAW264.7 cells ( n = 6). This induced robust upregulation of Trem2 , Spp1 , and Apoe transcripts. (E) Tubular cell debris increased both the number and proliferative activity of Arg1 + macrophages. Higher debris concentrations further increased both measures, suggesting proliferation scales with debris exposure ( n = 6). (F, G, H) Flow cytometry revealed increased Trem2 receptor intensity on Arg1 + macrophages and a higher proportion of Trem2 + Arg1 + macrophages after debris stimulation ( n = 6). (I) Levels of Spp1 and Apoe in culture supernatants were significantly elevated following debris treatment ( n = 8). (J) Schematic illustration of the experimental design. Mouse primary BMDMs were pretreated with IL-4 to induce differentiation toward an Arg1 high phenotype, followed by co-culture with renal tubular debris. (K) Western blot analysis showed that IL-4 stimulation markedly upregulated Arg1 protein expression in BMDMs ( n = 6). (L, M) RT-qPCR and Western blot analyses confirmed that renal tubular debris further induced the transcriptional and translational upregulation of Trem2 in Arg1 high BMDMs ( n = 4). (N) Renal tubular debris promoted the viability and proliferation of Arg1 high BMDMs in a concentration-dependent manner ( n = 6). Significance was evaluated using Student’s unpaired t test and one-way ANOVA followed by Tukey’s test. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001, ns , no significance.

Article Snippet: In the renal tubular cell debris–stimulated group, the TREM2 inhibitor TREM2-IN-1 (HY-160421, MedChemExpress) was added at a concentration of 5 μM to assess cell proliferative activity and apoptosis.

Techniques: Cell Culture, Activity Assay, Flow Cytometry, Co-Culture Assay, Western Blot, Expressing, Quantitative RT-PCR, Concentration Assay

Journal: Frontiers in Immunology

Article Title: Trem2 activation by renal tubular debris sustains Arg1 + macrophage survival and promotes tubular epithelial repair in renal ischemia–reperfusion injury

doi: 10.3389/fimmu.2026.1819941

Figure Lengend Snippet: Trem2 is essential for the survival and repair function of Arg1 + macrophages. (A–D) Establishment of stable Trem2 knockdown (KD) RAW264.7 cells using shRNA lentiviral transduction, confirmed by GFP fluorescence, qPCR, and Western blot ( n = 3-6). (E) Schematic illustration of the co-culture system of IL-4–pretreated Trem2 KD RAW264.7 cells with tubular cell debris. (F) Trem2 deficiency markedly impaired debris-induced proliferation of Arg1 + macrophages across both low and high debris concentrations ( n = 6). (G) Debris-induced expansion of Arg1 + macrophages was significantly reduced upon Trem2 Knockdown ( n = 6). (H, I) Apoptosis assays showed increased apoptosis of Arg1 + macrophages under Trem2 Knockdown ( n = 3). (J, K) Trem2 Knockdown attenuated IL-4–induced Arg1 expression, suggesting impaired polarization toward a pro-repair phenotype ( n = 3-6). (L–N) Conditioned medium from Trem2-sufficient Arg1 + macrophages promoted TCMK-1 cell proliferation and expansion, whereas Trem2 KD abolished this pro-regenerative effect ( n = 8). (O) Levels of spermidine and spermine in the supernatants of Arg1 + macrophages were increased upon stimulation with tubular debris and reduced by Trem2 knockdown ( n = 8). (P) Tubular debris stimulation increased HGF and VEGF levels in Arg1 + macrophage supernatants, which were reduced by Trem2 knockdown, while IL-10 levels remained unchanged ( n = 8). Significance was evaluated using Student’s unpaired t test, one-way ANOVA, or two-way ANOVA followed by Tukey’s test. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001, ns , no significance.

Article Snippet: In the renal tubular cell debris–stimulated group, the TREM2 inhibitor TREM2-IN-1 (HY-160421, MedChemExpress) was added at a concentration of 5 μM to assess cell proliferative activity and apoptosis.

Techniques: Knockdown, shRNA, Transduction, Fluorescence, Western Blot, Co-Culture Assay, Expressing

Journal: Frontiers in Immunology

Article Title: Trem2 activation by renal tubular debris sustains Arg1 + macrophage survival and promotes tubular epithelial repair in renal ischemia–reperfusion injury

doi: 10.3389/fimmu.2026.1819941

Figure Lengend Snippet: Inhibition of Trem2 reduces the survival of Arg1 high BMDMs and impairs their ability to promote renal tubular epithelial cell proliferation. (A) Schematic illustration of the experimental design: BMDMs were treated with TREM2-IN-1 in combination with IL-4 and subsequently co-cultured with renal tubular cell debris. (B) Western blot analysis confirmed that TREM2-IN-1 markedly downregulated Trem2 protein levels in Arg1 high BMDMs ( n = 6). (C) Tubular cell debris enhanced the viability of Arg1 high BMDMs, whereas TREM2-IN-1 treatment significantly reduced both BMDMs viability and BMDMs number ( n = 6). (D) Flow cytometry revealed that inhibition of Trem2 significantly decreased the survival rate of Arg1 high BMDMs and markedly increased apoptosis ( n = 3). (E) Schematic of the conditioned medium experiment: Culture supernatants were collected from Arg1 high BMDMs and applied to TCMK-1 cells. (F) Conditioned medium from BMDMs treated with IL-4 and renal tubular cell debris significantly promoted TCMK-1 cell proliferation, whereas the addition of TREM2-IN-1 markedly attenuated this pro-proliferative effect ( n = 6). (G) Measurement of Arg1 high BMDM-derived secreted factors: TREM2-IN-1 treatment significantly reduced the levels of spermidine, spermine, HGF, and VEGF in the conditioned medium, while IL-10 levels remained unchanged ( n = 6). Significance was evaluated using Student’s unpaired t test, one-way ANOVA, or two-way ANOVA followed by Tukey’s test. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001, ns , no significance.

Article Snippet: In the renal tubular cell debris–stimulated group, the TREM2 inhibitor TREM2-IN-1 (HY-160421, MedChemExpress) was added at a concentration of 5 μM to assess cell proliferative activity and apoptosis.

Techniques: Inhibition, Cell Culture, Western Blot, Flow Cytometry, Derivative Assay

Journal: Frontiers in Immunology

Article Title: Trem2 activation by renal tubular debris sustains Arg1 + macrophage survival and promotes tubular epithelial repair in renal ischemia–reperfusion injury

doi: 10.3389/fimmu.2026.1819941

Figure Lengend Snippet: Knockdown of Trem2 decreases the survival of Arg1 + macrophages via Pten activation and Bcl2 suppression. (A, B) RNA-seq comparing control and Trem2 knockdown Arg1 + macrophages co-cultured with tubular cell debris identified DEGs; FDR < 0.05, |Fold Change| > 1.5). (C) KEGG pathway enrichment revealed significant changes in efferocytosis and apoptosis pathways, indicating impaired debris clearance and altered apoptotic regulation upon Trem2 Knowdown. (D) Trem2 Knockdown downregulated anti-apoptotic proteins Bcl2 downstream of PI3K-AKT while upregulating the negative regulator Pten . (E) Protein-protein interaction network showed Pten links to multiple anti-apoptotic proteins. (F) Transcription factor analysis predicted Egr1 as a potential upstream regulator of Pten . (G, H) Western blot showing increased Pten and decreased Bcl2 expression in Trem2-knockdown Arg1 + macrophages ( n = 4). (I) Experimental design: macrophages were pretreated with VO-Ohpic (Pten inhibitor) and co-cultured with renal tubular debris. (J, K) VO-Ohpic treatment significantly inhibited Pten expression in Trem2-knockdown Arg1 + macrophages ( n = 6). (L, M) Under co-culture conditions, Bcl2 protein expression was restored in VO-Ohpic-treated cells ( n = 4). (N) VO-Ohpic treatment rescued proliferative activity and increased cell numbers in Trem2-knockdown Arg1 + macrophages compared with the vehicle group ( n = 6). (O, P) VO-Ohpic reduced late apoptosis and necrosis, and improved viability of Trem2-knockdown Arg1 + macrophages ( n = 6). Significance was evaluated using Student’s unpaired t test, one-way ANOVA, or two-way ANOVA followed by Tukey’s test and Mann–Whitney U test for non-parametric comparisons. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001, ns , no significance.

Article Snippet: In the renal tubular cell debris–stimulated group, the TREM2 inhibitor TREM2-IN-1 (HY-160421, MedChemExpress) was added at a concentration of 5 μM to assess cell proliferative activity and apoptosis.

Techniques: Knockdown, Activation Assay, RNA Sequencing, Control, Cell Culture, Western Blot, Expressing, Co-Culture Assay, Activity Assay, MANN-WHITNEY

Journal: Frontiers in Immunology

Article Title: Trem2 activation by renal tubular debris sustains Arg1 + macrophage survival and promotes tubular epithelial repair in renal ischemia–reperfusion injury

doi: 10.3389/fimmu.2026.1819941

Figure Lengend Snippet: Inhibition of Ttem2 reduces the viability of Arg1 high BMDMs by upregulating Pten and suppressing Bcl2. (A) Schematic illustration of the experimental design: IL-4–induced Arg1 high BMDMs were first treated with TREM2-IN-1 to inhibit Trem2, followed by treatment with the PTEN inhibitor VO-Ohpic, and subsequently co-cultured with renal tubular cell debris. (B, C) Western blot analysis showed that, compared with the control group, VO-Ohpic treatment significantly downregulated Pten protein expression in Arg1 high BMDMs and markedly upregulated the expression of the key anti-apoptotic protein Bcl2 ( n = 6). (D) VO-Ohpic treatment effectively reversed the TREM2-IN-1–induced reduction in cell viability and cell number of Arg1 high BMDMs ( n = 6). (E) Proposed mechanism: Tubular cell debris generated during IRI, in conjunction with Apoe released by Arg1 + macrophages, activates Trem2 and further upregulates its expression. Elevated Trem2 signaling suppresses Pten and upregulates the anti-apoptotic factor Bcl2, thereby promoting debris clearance, Arg1 + macrophage survival. Surviving Arg1 + macrophages release spermidine, spermine, HGF, and VEGF, which enhance renal tubular epithelial cell regeneration and repair. Significance was evaluated using Student’s unpaired t test and two-way ANOVA followed by Tukey’s test. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001, ns , no significance.

Article Snippet: In the renal tubular cell debris–stimulated group, the TREM2 inhibitor TREM2-IN-1 (HY-160421, MedChemExpress) was added at a concentration of 5 μM to assess cell proliferative activity and apoptosis.

Techniques: Inhibition, Cell Culture, Western Blot, Control, Expressing, Generated

Journal: The Journal of Headache and Pain

Article Title: TREM2 contributes to central sensitization through PI3K/Akt/mTOR-mediated autophagic dysfunction in a rat model of vestibular migraine

doi: 10.1186/s10194-026-02337-8

Figure Lengend Snippet: TREM2 upregulation and central sensitization induced by repeated NTG and rotational stimulation. Behavioral testing demonstrated significant alterations in multiple parameters following stimulation. Specifically, a significant decrease in the plantar pain threshold and tail-flick latency was observed in the VM and CM groups ( a , b ). In contrast, beam walking time and MSI were significantly increased in these groups ( c , d ). Data were analyzed by two-way ANOVA followed by Dunnett’s post hoc test and are presented as mean ± SEM ( n = 6). *p < 0.05, * *p < 0.01, ** *p < 0.001, *** *p < 0.0001 (*HC vs. VM, #HC vs. CM). Immunofluorescence staining showed colocalization of TREM2 (red) with Iba1 (microglia marker) and NeuN (neuronal marker) in the TCC ( e ) and VN ( g ), while CGRP was predominantly expressed in neurons ( i , k ). Scale bars = 1000 μm, 200 μm, and 20 μm. Arrows indicate sites of protein colocalization. Western blot analysis confirmed increased TREM2 ( f , h ), CGRP ( j , l ), c-Fos ( m – p ) expression in both the TCC and VN. Quantification data, presented as mean ± SEM ( n = 6), were analyzed by one-way ANOVA with Dunnett’s T3 post hoc test. *p < 0.05, * *p < 0.01, *** p < 0.001, **** p < 0.0001 compared with the HC group

Article Snippet: To assess the roles of TREM2 and mTOR in VM, the TREM2 inhibitor IA9 (25 mg/kg, Supplier: MCE, Cat. No. HY- P10136 ), TREM2 agonist COG1410 (1 mg/kg, Supplier: MCE, Cat. No. HY-P2136), and autophagy inducer rapamycin (2 mg/kg, Supplier: MCE, Cat. No. HY-10219) were administered intraperitoneally 30 min before each NTG or saline injection.

Techniques: Tail Flick Test, Immunofluorescence, Staining, Marker, Western Blot, Expressing

Journal: The Journal of Headache and Pain

Article Title: TREM2 contributes to central sensitization through PI3K/Akt/mTOR-mediated autophagic dysfunction in a rat model of vestibular migraine

doi: 10.1186/s10194-026-02337-8

Figure Lengend Snippet: Intraperitoneal administration of rapamycin or IA9 alleviates central sensitization in VM rats. ( a – d ) Behavioral tests showing reduced mechanical and thermal pain thresholds, prolonged beam walking time, and increased MSI in the VM group, all of which were ameliorated by IA9 or RAPA treatment. Data were analyzed by two-way ANOVA followed by Dunnett’s post hoc test and are presented as mean ± SEM ( n = 6). *p < 0.05, * *p < 0.01, ** *p < 0.001, *** *p < 0.0001 (*VEH vs. VM, #VM vs. VM+IA9, ^VM vs. VM+RAPA). ( e – h , m – t ) Western blots showing increased TREM2, CGRP, c-Fos expression and p-mTOR/mTOR ratio in the TCC and VN of the VM group, which were reversed by IA9 or RAPA treatment. Data were analyzed by one-way ANOVA followed by Dunnett’s T3 or Tukey’s post hoc test and are presented as mean ± SEM ( n = 6). *p < 0.05, * *p < 0.01, ** *p < 0.001, *** *p < 0.0001. ( i – l ) Immunofluorescence staining showing enhanced CGRP fluorescence intensity in the TCC and VN of the VM group, which were significantly reduced by IA9 or RAPA treatment. Data were analyzed by one-way ANOVA followed by Tukey’s post hoc test and are presented as mean ± SEM ( n = 4). *p < 0.05, * *p < 0.01, ** *p < 0.001, *** *p < 0.0001. Scale bars = 200 μm

Article Snippet: To assess the roles of TREM2 and mTOR in VM, the TREM2 inhibitor IA9 (25 mg/kg, Supplier: MCE, Cat. No. HY- P10136 ), TREM2 agonist COG1410 (1 mg/kg, Supplier: MCE, Cat. No. HY-P2136), and autophagy inducer rapamycin (2 mg/kg, Supplier: MCE, Cat. No. HY-10219) were administered intraperitoneally 30 min before each NTG or saline injection.

Techniques: Western Blot, Expressing, Immunofluorescence, Staining, Fluorescence

Journal: The Journal of Headache and Pain

Article Title: TREM2 contributes to central sensitization through PI3K/Akt/mTOR-mediated autophagic dysfunction in a rat model of vestibular migraine

doi: 10.1186/s10194-026-02337-8

Figure Lengend Snippet: TREM2 blockade activates autophagy and inhibits the PI3K/Akt/mTOR pathway in VM rats. ( a – c , e – g ) WB and quantification of PI3K, p-Akt, and p-mTOR expression in the TCC and VN. ( d , h ) WB and quantification of p62 expression in the TCC and VN. ( i – l ) Quantification of the LC3-II/LC3-I ratio. Data are presented as mean ± SEM ( n = 6) and analyzed by one-way ANOVA followed by Dunnett’s T3 post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001

Article Snippet: To assess the roles of TREM2 and mTOR in VM, the TREM2 inhibitor IA9 (25 mg/kg, Supplier: MCE, Cat. No. HY- P10136 ), TREM2 agonist COG1410 (1 mg/kg, Supplier: MCE, Cat. No. HY-P2136), and autophagy inducer rapamycin (2 mg/kg, Supplier: MCE, Cat. No. HY-10219) were administered intraperitoneally 30 min before each NTG or saline injection.

Techniques: Expressing

Journal: The Journal of Headache and Pain

Article Title: TREM2 contributes to central sensitization through PI3K/Akt/mTOR-mediated autophagic dysfunction in a rat model of vestibular migraine

doi: 10.1186/s10194-026-02337-8

Figure Lengend Snippet: TREM2 blockade alleviated neuroinflammation in VM rats. ( a – h ) WB and quantification of NLRP3, ASC, cleaved caspase-1, and IL-1β expression in the TCC and VN. ( i – r ) Immunofluorescence detection of the activation status of IBA1-positive microglia in the TNC and VN. Data are presented as mean ± SEM ( n = 6) and analyzed by one-way ANOVA followed by Dunnett’s T3 or Turkey post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. Scale bar = 20 μm

Article Snippet: To assess the roles of TREM2 and mTOR in VM, the TREM2 inhibitor IA9 (25 mg/kg, Supplier: MCE, Cat. No. HY- P10136 ), TREM2 agonist COG1410 (1 mg/kg, Supplier: MCE, Cat. No. HY-P2136), and autophagy inducer rapamycin (2 mg/kg, Supplier: MCE, Cat. No. HY-10219) were administered intraperitoneally 30 min before each NTG or saline injection.

Techniques: Expressing, Immunofluorescence, Activation Assay

Journal: The Journal of Headache and Pain

Article Title: TREM2 contributes to central sensitization through PI3K/Akt/mTOR-mediated autophagic dysfunction in a rat model of vestibular migraine

doi: 10.1186/s10194-026-02337-8

Figure Lengend Snippet: Activation of TREM2 by COG1410 exacerbates central sensitization in VM rats, which is reversed by RAPA. ( a – d ) Behavioral test results. Data are presented as mean ± SEM ( n = 3) and were analyzed by two-way ANOVA followed by Tukey’s post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001 (*VEH vs. VM, #VEH vs. VM+COG, ^VM+COG vs. VM+COG+RAPA). ( e – h ) WB and quantification of TREM2 and CGRP protein expression in the TCC and VN. Data are presented as mean ± SEM ( n = 3) and analyzed by one-way ANOVA followed by Tukey’s post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001

Article Snippet: To assess the roles of TREM2 and mTOR in VM, the TREM2 inhibitor IA9 (25 mg/kg, Supplier: MCE, Cat. No. HY- P10136 ), TREM2 agonist COG1410 (1 mg/kg, Supplier: MCE, Cat. No. HY-P2136), and autophagy inducer rapamycin (2 mg/kg, Supplier: MCE, Cat. No. HY-10219) were administered intraperitoneally 30 min before each NTG or saline injection.

Techniques: Activation Assay, Expressing

Journal: The Journal of Headache and Pain

Article Title: TREM2 contributes to central sensitization through PI3K/Akt/mTOR-mediated autophagic dysfunction in a rat model of vestibular migraine

doi: 10.1186/s10194-026-02337-8

Figure Lengend Snippet: TREM2 activation regulates autophagic flux and NLRP3 inflammasome activation in VM rats via the PI3K/Akt/mTOR pathway. ( a – c , i – k ) Representative Western blots and quantification of PI3K, p-Akt, and p-mTOR expression in the TCC and VN regions. ( d – e , l – m ) Representative Western blots and quantification of LC3-II/LC3-I ratio and p62 expression. ( f – h , n – t ) Representative Western blots and quantification of NLRP3, ASC, cleaved caspase-1, and IL-1β expression. Data are presented as mean ± SEM ( n = 3). Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. *p < 0.05, * *p < 0.01, ** *p < 0.001, *** *p < 0.0001

Article Snippet: To assess the roles of TREM2 and mTOR in VM, the TREM2 inhibitor IA9 (25 mg/kg, Supplier: MCE, Cat. No. HY- P10136 ), TREM2 agonist COG1410 (1 mg/kg, Supplier: MCE, Cat. No. HY-P2136), and autophagy inducer rapamycin (2 mg/kg, Supplier: MCE, Cat. No. HY-10219) were administered intraperitoneally 30 min before each NTG or saline injection.

Techniques: Activation Assay, Western Blot, Expressing

Journal: The Journal of Headache and Pain

Article Title: TREM2 contributes to central sensitization through PI3K/Akt/mTOR-mediated autophagic dysfunction in a rat model of vestibular migraine

doi: 10.1186/s10194-026-02337-8

Figure Lengend Snippet: TREM2 upregulation and central sensitization induced by repeated NTG and rotational stimulation. Behavioral testing demonstrated significant alterations in multiple parameters following stimulation. Specifically, a significant decrease in the plantar pain threshold and tail-flick latency was observed in the VM and CM groups ( a , b ). In contrast, beam walking time and MSI were significantly increased in these groups ( c , d ). Data were analyzed by two-way ANOVA followed by Dunnett’s post hoc test and are presented as mean ± SEM ( n = 6). *p < 0.05, * *p < 0.01, ** *p < 0.001, *** *p < 0.0001 (*HC vs. VM, #HC vs. CM). Immunofluorescence staining showed colocalization of TREM2 (red) with Iba1 (microglia marker) and NeuN (neuronal marker) in the TCC ( e ) and VN ( g ), while CGRP was predominantly expressed in neurons ( i , k ). Scale bars = 1000 μm, 200 μm, and 20 μm. Arrows indicate sites of protein colocalization. Western blot analysis confirmed increased TREM2 ( f , h ), CGRP ( j , l ), c-Fos ( m – p ) expression in both the TCC and VN. Quantification data, presented as mean ± SEM ( n = 6), were analyzed by one-way ANOVA with Dunnett’s T3 post hoc test. *p < 0.05, * *p < 0.01, *** p < 0.001, **** p < 0.0001 compared with the HC group

Article Snippet: To assess the roles of TREM2 and mTOR in VM, the TREM2 inhibitor IA9 (25 mg/kg, Supplier: MCE, Cat. No. HY- P10136 ), TREM2 agonist COG1410 (1 mg/kg, Supplier: MCE, Cat. No. HY-P2136), and autophagy inducer rapamycin (2 mg/kg, Supplier: MCE, Cat. No. HY-10219) were administered intraperitoneally 30 min before each NTG or saline injection.

Techniques: Tail Flick Test, Immunofluorescence, Staining, Marker, Western Blot, Expressing

Journal: The Journal of Headache and Pain

Article Title: TREM2 contributes to central sensitization through PI3K/Akt/mTOR-mediated autophagic dysfunction in a rat model of vestibular migraine

doi: 10.1186/s10194-026-02337-8

Figure Lengend Snippet: Intraperitoneal administration of rapamycin or IA9 alleviates central sensitization in VM rats. ( a – d ) Behavioral tests showing reduced mechanical and thermal pain thresholds, prolonged beam walking time, and increased MSI in the VM group, all of which were ameliorated by IA9 or RAPA treatment. Data were analyzed by two-way ANOVA followed by Dunnett’s post hoc test and are presented as mean ± SEM ( n = 6). *p < 0.05, * *p < 0.01, ** *p < 0.001, *** *p < 0.0001 (*VEH vs. VM, #VM vs. VM+IA9, ^VM vs. VM+RAPA). ( e – h , m – t ) Western blots showing increased TREM2, CGRP, c-Fos expression and p-mTOR/mTOR ratio in the TCC and VN of the VM group, which were reversed by IA9 or RAPA treatment. Data were analyzed by one-way ANOVA followed by Dunnett’s T3 or Tukey’s post hoc test and are presented as mean ± SEM ( n = 6). *p < 0.05, * *p < 0.01, ** *p < 0.001, *** *p < 0.0001. ( i – l ) Immunofluorescence staining showing enhanced CGRP fluorescence intensity in the TCC and VN of the VM group, which were significantly reduced by IA9 or RAPA treatment. Data were analyzed by one-way ANOVA followed by Tukey’s post hoc test and are presented as mean ± SEM ( n = 4). *p < 0.05, * *p < 0.01, ** *p < 0.001, *** *p < 0.0001. Scale bars = 200 μm

Article Snippet: To assess the roles of TREM2 and mTOR in VM, the TREM2 inhibitor IA9 (25 mg/kg, Supplier: MCE, Cat. No. HY- P10136 ), TREM2 agonist COG1410 (1 mg/kg, Supplier: MCE, Cat. No. HY-P2136), and autophagy inducer rapamycin (2 mg/kg, Supplier: MCE, Cat. No. HY-10219) were administered intraperitoneally 30 min before each NTG or saline injection.

Techniques: Western Blot, Expressing, Immunofluorescence, Staining, Fluorescence

Journal: The Journal of Headache and Pain

Article Title: TREM2 contributes to central sensitization through PI3K/Akt/mTOR-mediated autophagic dysfunction in a rat model of vestibular migraine

doi: 10.1186/s10194-026-02337-8

Figure Lengend Snippet: TREM2 blockade activates autophagy and inhibits the PI3K/Akt/mTOR pathway in VM rats. ( a – c , e – g ) WB and quantification of PI3K, p-Akt, and p-mTOR expression in the TCC and VN. ( d , h ) WB and quantification of p62 expression in the TCC and VN. ( i – l ) Quantification of the LC3-II/LC3-I ratio. Data are presented as mean ± SEM ( n = 6) and analyzed by one-way ANOVA followed by Dunnett’s T3 post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001

Article Snippet: To assess the roles of TREM2 and mTOR in VM, the TREM2 inhibitor IA9 (25 mg/kg, Supplier: MCE, Cat. No. HY- P10136 ), TREM2 agonist COG1410 (1 mg/kg, Supplier: MCE, Cat. No. HY-P2136), and autophagy inducer rapamycin (2 mg/kg, Supplier: MCE, Cat. No. HY-10219) were administered intraperitoneally 30 min before each NTG or saline injection.

Techniques: Expressing

Journal: The Journal of Headache and Pain

Article Title: TREM2 contributes to central sensitization through PI3K/Akt/mTOR-mediated autophagic dysfunction in a rat model of vestibular migraine

doi: 10.1186/s10194-026-02337-8

Figure Lengend Snippet: TREM2 blockade alleviated neuroinflammation in VM rats. ( a – h ) WB and quantification of NLRP3, ASC, cleaved caspase-1, and IL-1β expression in the TCC and VN. ( i – r ) Immunofluorescence detection of the activation status of IBA1-positive microglia in the TNC and VN. Data are presented as mean ± SEM ( n = 6) and analyzed by one-way ANOVA followed by Dunnett’s T3 or Turkey post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. Scale bar = 20 μm

Article Snippet: To assess the roles of TREM2 and mTOR in VM, the TREM2 inhibitor IA9 (25 mg/kg, Supplier: MCE, Cat. No. HY- P10136 ), TREM2 agonist COG1410 (1 mg/kg, Supplier: MCE, Cat. No. HY-P2136), and autophagy inducer rapamycin (2 mg/kg, Supplier: MCE, Cat. No. HY-10219) were administered intraperitoneally 30 min before each NTG or saline injection.

Techniques: Expressing, Immunofluorescence, Activation Assay

Journal: The Journal of Headache and Pain

Article Title: TREM2 contributes to central sensitization through PI3K/Akt/mTOR-mediated autophagic dysfunction in a rat model of vestibular migraine

doi: 10.1186/s10194-026-02337-8

Figure Lengend Snippet: Activation of TREM2 by COG1410 exacerbates central sensitization in VM rats, which is reversed by RAPA. ( a – d ) Behavioral test results. Data are presented as mean ± SEM ( n = 3) and were analyzed by two-way ANOVA followed by Tukey’s post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001 (*VEH vs. VM, #VEH vs. VM+COG, ^VM+COG vs. VM+COG+RAPA). ( e – h ) WB and quantification of TREM2 and CGRP protein expression in the TCC and VN. Data are presented as mean ± SEM ( n = 3) and analyzed by one-way ANOVA followed by Tukey’s post hoc test. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001

Article Snippet: To assess the roles of TREM2 and mTOR in VM, the TREM2 inhibitor IA9 (25 mg/kg, Supplier: MCE, Cat. No. HY- P10136 ), TREM2 agonist COG1410 (1 mg/kg, Supplier: MCE, Cat. No. HY-P2136), and autophagy inducer rapamycin (2 mg/kg, Supplier: MCE, Cat. No. HY-10219) were administered intraperitoneally 30 min before each NTG or saline injection.

Techniques: Activation Assay, Expressing

Journal: The Journal of Headache and Pain

Article Title: TREM2 contributes to central sensitization through PI3K/Akt/mTOR-mediated autophagic dysfunction in a rat model of vestibular migraine

doi: 10.1186/s10194-026-02337-8

Figure Lengend Snippet: TREM2 activation regulates autophagic flux and NLRP3 inflammasome activation in VM rats via the PI3K/Akt/mTOR pathway. ( a – c , i – k ) Representative Western blots and quantification of PI3K, p-Akt, and p-mTOR expression in the TCC and VN regions. ( d – e , l – m ) Representative Western blots and quantification of LC3-II/LC3-I ratio and p62 expression. ( f – h , n – t ) Representative Western blots and quantification of NLRP3, ASC, cleaved caspase-1, and IL-1β expression. Data are presented as mean ± SEM ( n = 3). Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. *p < 0.05, * *p < 0.01, ** *p < 0.001, *** *p < 0.0001

Article Snippet: To assess the roles of TREM2 and mTOR in VM, the TREM2 inhibitor IA9 (25 mg/kg, Supplier: MCE, Cat. No. HY- P10136 ), TREM2 agonist COG1410 (1 mg/kg, Supplier: MCE, Cat. No. HY-P2136), and autophagy inducer rapamycin (2 mg/kg, Supplier: MCE, Cat. No. HY-10219) were administered intraperitoneally 30 min before each NTG or saline injection.

Techniques: Activation Assay, Western Blot, Expressing