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Deletion of Slc9a1 in Cx3cr1+ cells stimulated microglial subcluster CREB1 signaling and microglia-oligodendrocyte crosstalk.
Song, Shanshan; Oft, Helena; Metwally, Shamseldin; Paruchuri, Satya; Bielanin, John; Fiesler, Victoria; Sneiderman, Chaim; Kohanbash, Gary; Sun, Dandan.
Afiliación
  • Song S; Department of Neurology, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, PA, 15213, USA. songs2@upmc.edu.
  • Oft H; Pittsburgh Institute for Neurodegenerative Disorders, University of Pittsburgh, Pittsburgh, PA, USA. songs2@upmc.edu.
  • Metwally S; Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA, 15213, USA. songs2@upmc.edu.
  • Paruchuri S; Department of Neurology, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, PA, 15213, USA.
  • Bielanin J; Pittsburgh Institute for Neurodegenerative Disorders, University of Pittsburgh, Pittsburgh, PA, USA.
  • Fiesler V; Department of Neurology, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, PA, 15213, USA.
  • Sneiderman C; Pittsburgh Institute for Neurodegenerative Disorders, University of Pittsburgh, Pittsburgh, PA, USA.
  • Kohanbash G; Department of Neurology, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, PA, 15213, USA.
  • Sun D; Pittsburgh Institute for Neurodegenerative Disorders, University of Pittsburgh, Pittsburgh, PA, USA.
J Neuroinflammation ; 21(1): 69, 2024 Mar 20.
Article en En | MEDLINE | ID: mdl-38509618
ABSTRACT
Microglial Na/H exchanger-1 (NHE1) protein, encoded by Slc9a1, plays a role in white matter demyelination of ischemic stroke brains. To explore underlying mechanisms, we conducted single cell RNA-seq transcriptome analysis in conditional Slc9a1 knockout (cKO) and wild-type (WT) mouse white matter tissues at 3 days post-stroke. Compared to WT, Nhe1 cKO brains expanded a microglial subgroup with elevated transcription of white matter myelination genes including Spp1, Lgals3, Gpnmb, and Fabp5. This subgroup also exhibited more acidic pHi and significantly upregulated CREB signaling detected by ingenuity pathway analysis and flow cytometry. Moreover, the Nhe1 cKO white matter tissues showed enrichment of a corresponding oligodendrocyte subgroup, with pro-phagocytosis and lactate shuffling gene expression, where activated CREB signaling is a likely upstream regulator. These findings demonstrate that attenuation of NHE1-mediated H+ extrusion acidifies microglia/macrophage and may underlie the stimulation of CREB1 signaling, giving rise to restorative microglia-oligodendrocyte interactions for remyelination.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Microglía / Intercambiador 1 de Sodio-Hidrógeno Límite: Animals Idioma: En Revista: J Neuroinflammation Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Microglía / Intercambiador 1 de Sodio-Hidrógeno Límite: Animals Idioma: En Revista: J Neuroinflammation Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido