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Th17 cell mediated oligodendrocyte precursor cell arrest drives hippocampal demyelination in diabetic cognitive dysfunction.

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Τίτλος: Th17 cell mediated oligodendrocyte precursor cell arrest drives hippocampal demyelination in diabetic cognitive dysfunction.
Συγγραφείς: 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.
Πηγή: Clinical science (London, England : 1979) [Clin Sci (Lond)] 2026 Jul 15; Vol. 140 (7), pp. 1521-1534.
Τύπος έκδοσης: Journal Article; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: 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.
Ιατρικοί όροι (MeSH): 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
Περίληψη: 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
Βάση Δεδομένων: MEDLINE
FullText Text:
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DbLabel: MEDLINE
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AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
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  Data: Th17 cell mediated oligodendrocyte precursor cell arrest drives hippocampal demyelination in diabetic cognitive dysfunction.
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  Data: <searchLink fieldCode="AU" term="%22Hu+JW%22">Hu JW</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Yu+HD%22">Yu HD</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Yu+SX%22">Yu SX</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Liu+WQ%22">Liu WQ</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Wang+YF%22">Wang YF</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Wang+YL%22">Wang YL</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Chen+XY%22">Chen XY</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Miao+QL%22">Miao QL</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Yuan+YR%22">Yuan YR</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Dai+W%22">Dai W</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Liu+MR%22">Liu MR</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Zhang+N%22">Zhang N</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Sui+JH%22">Sui JH</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Liu+XZ%22">Liu XZ</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Shan+W%22">Shan W</searchLink>; Department of Anatomy, Histology and Embryology, Jinzhou Medical University, Jinzhou, PR China.<br /><searchLink fieldCode="AU" term="%22Zuo+ZF%22">Zuo ZF</searchLink>; 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.
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  Data: <searchLink fieldCode="MM" term="%22Hippocampus%22">Hippocampus*</searchLink>/<searchLink fieldCode="MM" term="%22Hippocampus+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Hippocampus%22">Hippocampus*</searchLink>/<searchLink fieldCode="MM" term="%22Hippocampus+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Hippocampus%22">Hippocampus*</searchLink>/<searchLink fieldCode="MM" term="%22Hippocampus+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Oligodendrocyte+Precursor+Cells%22">Oligodendrocyte Precursor Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Oligodendrocyte+Precursor+Cells+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Oligodendrocyte+Precursor+Cells%22">Oligodendrocyte Precursor Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Oligodendrocyte+Precursor+Cells+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Oligodendrocyte+Precursor+Cells%22">Oligodendrocyte Precursor Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Oligodendrocyte+Precursor+Cells+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Th17+Cells%22">Th17 Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Th17+Cells+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Th17+Cells%22">Th17 Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Th17+Cells+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Demyelinating+Diseases%22">Demyelinating Diseases*</searchLink>/<searchLink fieldCode="MM" term="%22Demyelinating+Diseases+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Demyelinating+Diseases%22">Demyelinating Diseases*</searchLink>/<searchLink fieldCode="MM" term="%22Demyelinating+Diseases+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Demyelinating+Diseases%22">Demyelinating Diseases*</searchLink>/<searchLink fieldCode="MM" term="%22Demyelinating+Diseases+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Cognitive+Dysfunction%22">Cognitive Dysfunction*</searchLink>/<searchLink fieldCode="MM" term="%22Cognitive+Dysfunction+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Cognitive+Dysfunction%22">Cognitive Dysfunction*</searchLink>/<searchLink fieldCode="MM" term="%22Cognitive+Dysfunction+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Cognitive+Dysfunction%22">Cognitive Dysfunction*</searchLink>/<searchLink fieldCode="MM" term="%22Cognitive+Dysfunction+etiology%22">etiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Cognitive+Dysfunction%22">Cognitive Dysfunction*</searchLink>/<searchLink fieldCode="MM" term="%22Cognitive+Dysfunction+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Diabetes+Mellitus%2C+Experimental%22">Diabetes Mellitus, Experimental*</searchLink>/<searchLink fieldCode="MM" term="%22Diabetes+Mellitus%2C+Experimental+complications%22">complications</searchLink> <br /><searchLink fieldCode="MM" term="%22Diabetes+Mellitus%2C+Experimental%22">Diabetes Mellitus, Experimental*</searchLink>/<searchLink fieldCode="MM" term="%22Diabetes+Mellitus%2C+Experimental+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Diabetes+Mellitus%2C+Experimental%22">Diabetes Mellitus, Experimental*</searchLink>/<searchLink fieldCode="MM" term="%22Diabetes+Mellitus%2C+Experimental+immunology%22">immunology</searchLink> <br /><searchLink fieldCode="MM" term="%22Diabetes+Mellitus%2C+Experimental%22">Diabetes Mellitus, Experimental*</searchLink>/<searchLink fieldCode="MM" term="%22Diabetes+Mellitus%2C+Experimental+chemically+induced%22">chemically induced</searchLink><br /><searchLink fieldCode="MH" term="%22Interleukin-17%22">Interleukin-17</searchLink>/<searchLink fieldCode="MH" term="%22Interleukin-17+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Interleukin-17%22">Interleukin-17</searchLink>/<searchLink fieldCode="MH" term="%22Interleukin-17+immunology%22">immunology</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%2C+Inbred+C57BL%22">Mice, Inbred C57BL</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%22">Mice</searchLink> ; <searchLink fieldCode="MH" term="%22Cognition%22">Cognition</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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.<br /> (© 2026 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
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  Data: LJKMZ20221241 Foundation of Liaoning Province Education Administration; 2023-MS-312 Natural Science Foundation of Liaoning Province
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  Data: <i>Keywords: </i>Diabetic cognitive dysfunction; ERK1/2; IL-17A; demyelination; oligodendrocyte precursor cell
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  Data: 0 (Interleukin-17)<br />0 (Il17a protein, mouse)
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  Data: <i>Date Created: </i>20260309 <i>Date Completed: </i>20260629 <i>Latest Revision: </i>20260709
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  Data: 10.1042/CS20257295
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        Text: English
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        StartPage: 1521
    Subjects:
      – SubjectFull: Interleukin-17 metabolism
        Type: general
      – SubjectFull: Interleukin-17 immunology
        Type: general
      – SubjectFull: Animals
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      – SubjectFull: Hippocampus metabolism
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      – SubjectFull: Hippocampus pathology
        Type: general
      – SubjectFull: Hippocampus immunology
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      – SubjectFull: Oligodendrocyte Precursor Cells metabolism
        Type: general
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      – SubjectFull: Cognitive Dysfunction etiology
        Type: general
      – SubjectFull: Cognitive Dysfunction pathology
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      – SubjectFull: Diabetes Mellitus, Experimental complications
        Type: general
      – SubjectFull: Diabetes Mellitus, Experimental metabolism
        Type: general
      – SubjectFull: Diabetes Mellitus, Experimental immunology
        Type: general
      – SubjectFull: Diabetes Mellitus, Experimental chemically induced
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      – TitleFull: Th17 cell mediated oligodendrocyte precursor cell arrest drives hippocampal demyelination in diabetic cognitive dysfunction.
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            – Type: issue
              Value: 7
          Titles:
            – TitleFull: Clinical science (London, England : 1979)
              Type: main
ResultId 1