Academic Journal
Th17 cell mediated oligodendrocyte precursor cell arrest drives hippocampal demyelination in diabetic cognitive dysfunction.
| Title: | Th17 cell mediated oligodendrocyte precursor cell arrest drives hippocampal demyelination in diabetic cognitive dysfunction. |
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| Authors: | Hu JW; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China., Yu HD; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China., Yu SX; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China., Liu WQ; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China., Wang YF; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China., Wang YL; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China., Chen XY; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China., Miao QL; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China., Yuan YR; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China., Dai W; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China., Liu MR; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China., Zhang N; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China., Sui JH; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China., Liu XZ; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China., Shan W; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China., Zuo ZF; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.; Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou 121001, PR China. |
| Source: | Clinical science (London, England : 1979) [Clin Sci (Lond)] 2026 Jul 15; Vol. 140 (7), pp. 1521-1534. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Portland Press on behalf of the Medical Research Society and the Biochemical Society Country of Publication: England NLM ID: 7905731 Publication Model: Print Cited Medium: Internet ISSN: 1470-8736 (Electronic) Linking ISSN: 01435221 NLM ISO Abbreviation: Clin Sci (Lond) Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : Portland Press on behalf of the Medical Research Society and the Biochemical Society Original Publication: London, Medical Research Society. |
| MeSH Terms: | Hippocampus*/metabolism , Hippocampus*/pathology , Hippocampus*/immunology , Oligodendrocyte Precursor Cells*/metabolism , Oligodendrocyte Precursor Cells*/immunology , Oligodendrocyte Precursor Cells*/pathology , Th17 Cells*/metabolism , Th17 Cells*/immunology , Demyelinating Diseases*/metabolism , Demyelinating Diseases*/pathology , Demyelinating Diseases*/immunology , Cognitive Dysfunction*/metabolism , Cognitive Dysfunction*/immunology , Cognitive Dysfunction*/etiology , Cognitive Dysfunction*/pathology , Diabetes Mellitus, Experimental*/complications , Diabetes Mellitus, Experimental*/metabolism , Diabetes Mellitus, Experimental*/immunology , Diabetes Mellitus, Experimental*/chemically induced, Interleukin-17/metabolism ; Interleukin-17/immunology ; Animals ; Male ; Mice, Inbred C57BL ; Mice ; Cognition |
| Abstract: | Demyelination is pivotal in diabetic cognitive dysfunction, with Th17 cells gaining attention, yet their hippocampal infiltration and mechanisms in diabetes remain unelucidated. Using streptozotocin-induced diabetic mice, we demonstrated Th17 cell infiltration and elevated IL-17A in the hippocampus via CD4/IL-17A immunofluorescence and Western blot. Administering IL-17A neutralizing antibodies (NAbs) improved cognitive performance (Morris water maze: reduced escape latency, increased platform crossings/target quadrant time); attenuated neuroinflammation (reduced IL-17A, TNF-α, IL-1β, and IL-6; increased IL-10 and IL-4; decreased microglial activation/IBA-1); restored blood-brain barrier integrity (increased ZO-1 and occludin); and promoted remyelination (increased MBP and CNPase; decreased NG2 and Olig2; Luxol fast blue). IL-17A NAbs also enhanced phosphorylated ERK1/2. Crucially, co-treatment with the ERK inhibitor PD98059 partially reversed the protective effects of IL-17A NAbs on these parameters. These findings indicate that IL-17A, secreted by infiltrating Th17 cells, exacerbates hippocampal demyelination in DCD by inhibiting oligodendrocyte precursor cell maturation via suppression of the ERK1/2 pathway and concurrently activating microglia to amplify neuroinflammation, ultimately driving cognitive impairment. (© 2026 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.) |
| Grant Information: | LJKMZ20221241 Foundation of Liaoning Province Education Administration; 2023-MS-312 Natural Science Foundation of Liaoning Province |
| Contributed Indexing: | Keywords: Diabetic cognitive dysfunction; ERK1/2; IL-17A; demyelination; oligodendrocyte precursor cell |
| Substance Nomenclature: | 0 (Interleukin-17) 0 (Il17a protein, mouse) |
| Entry Date(s): | Date Created: 20260309 Date Completed: 20260629 Latest Revision: 20260709 |
| Update Code: | 20260711 |
| DOI: | 10.1042/CS20257295 |
| PMID: | 41797721 |
| Database: | MEDLINE |
| ISSN: | 1470-8736 |
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| DOI: | 10.1042/CS20257295 |