In the central nervous system, major histocompatibility complex class I (MHCI) molecules are mainly expressed in neurons, and neuronal MHCI have roles in synapse elimination and plasticity. However, the pathophysiological significance of astroglial MHCI remains unclear. We herein demonstrate that MHCI expression is up-regulated in astrocytes in the medial prefrontal cortex (mPFC) following systemic immune activation by an intraperitoneal injection of polyinosinic-polycytidylic acid (polyI:C) or hydrodynamic interferon (IFN)-γ gene delivery in male C57/BL6J mice. In cultured astrocytes, MHCI/H-2D largely co-localized with exosomes. To investigate the role of astroglial MHCI, H-2D, or sH-2D was expressed in the mPFC of male C57/BL6J mice using an adeno-associated virus vector under the control of a glial fibrillary acidic protein promoter. The expression of astroglial MHCI in the mPFC impaired sociability and recognition memory in mice. Regarding neuropathological changes, MHCI expression in astrocytes significantly activated microglial cells, decreased parvalbumin-positive cell numbers, and reduced dendritic spine density in the mPFC. A treatment with GW4869 that impairs exosome synthesis ameliorated these behavioral and neuropathological changes. These results suggest that the overexpression of MHCI in astrocytes affects microglial proliferation as well as neuronal numbers and spine densities, thereby leading to social and cognitive deficits in mice, possibly via exosomes created by astrocytes.
Pubmed ID: 29380419 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal targets IgG (H+L)
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis polyclonal targets mouse
View all literature mentionsThis polyclonal targets Goat IgG
View all literature mentionsThis monoclonal targets α-Tubulin
View all literature mentionsThis polyclonal targets CD63
View all literature mentionsThis monoclonal targets GM130
View all literature mentionsThis monoclonal targets Mouse CD107a
View all literature mentionsThis monoclonal targets IGF2R
View all literature mentionsThis monoclonal targets EEA1
View all literature mentionsThis polyclonal targets HA-probe
View all literature mentionsThis polyclonal targets Mouse IgG (H+L)
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis monoclonal targets CD8
View all literature mentionsThis polyclonal targets Parvalbumin
View all literature mentionsThis monoclonal targets Mouse MHC CLASS I H-2b/d/p/q/w16
View all literature mentionsThis monoclonal targets CD68
View all literature mentionsThis polyclonal targets Iba1
View all literature mentionsThis monoclonal targets Human Neuregulin-1 / NRG1
View all literature mentionsThis monoclonal targets GFAP
View all literature mentionsThis polyclonal targets GFP : Trial Size
View all literature mentionsThis unknown targets Sheep IgG
View all literature mentionsThis polyclonal targets Rabbit NeuN (polyclonal)
View all literature mentionsThis polyclonal targets Mouse GFAP
View all literature mentionsThis unknown targets Digoxigenin
View all literature mentionsCell line C8-D1A is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentions