Conditional deletion of beta1-integrin in astroglia causes partial reactive gliosis.
Astrocytes play many pivotal roles in the adult brain, including their reaction to injury. A hallmark of astrocytes is the contact of their endfeet with the basement membrane surrounding blood vessels, but still relatively little is known about the signaling mediated at the contact site. Here, we examine the role of beta1-integrin at this interface by its conditional deletion using different Cre lines. Thereby, the protein was reduced only at postnatal stages either in both glia and neurons or specifically only in neurons. Strikingly, only the former resulted in reactive gliosis, with the hallmarks of reactive astrocytes comprising astrocyte hypertrophy and up-regulation of the intermediate filaments GFAP and vimentin as well as pericellular components, such as Tenascin-C and the DSD-1 proteoglycan. In addition, we also observed to a certain degree a non-cell autonomous activation of microglial cells after conditional beta1-integrin deletion. However, these reactive astrocytes did not divide, suggesting that the loss of beta1-integrin-mediated signaling is not sufficient to elicit proliferation of these cells as observed after brain injury. Interestingly, this partial reactive gliosis appeared in the absence of cell death and blood brain barrier disturbances. As these effects did not appear after neuron-specific deletion of beta1-integrin, we conclude that beta1-integrin-mediated signaling in astrocytes is required to promote their acquisition of a mature, nonreactive state. Alterations in beta1-integrin-mediated signaling may hence be implicated in eliciting specific aspects of reactive gliosis after injury.
Department of Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, Munich, Germany.
Stefanie
S
Robel
Tetsuji
T
Mori
Saida
S
Zoubaa
Jürgen
J
Schlegel
Svetlana
S
Sirko
Andreas
A
Faissner
Sandra
S
Goebbels
Leda
L
Dimou
Magdalena
M
Götz
D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D001253:Astrocytes / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001812:Blood-Brain Barrier / Q000503:physiopathology; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D049029:Dystrophin-Associated Proteins / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein; D005911:Gliosis / Q000235:genetics*; D019012:Integrin beta1 / Q000235:genetics*; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009419:Nerve Tissue Proteins / Q000235:genetics; D016548:Prosencephalon / Q000473:pathology
D051401:Aquaporin 4; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D049029:Dystrophin-Associated Proteins; D005353:Fibronectins; D005904:Glial Fibrillary Acidic Protein; D019012:Integrin beta1; D007797:Laminin; D009419:Nerve Tissue Proteins; C110701:Neurod6 protein, mouse; C098885:dystrobrevin; C528900:glial fibrillary astrocytic protein, mouse