title: Astrocyte activation is suppressed in both normal and injured brain by FGF signaling.
abstract: In the brain, astrocytes are multifunctional cells that react to insults and contain damage. However, excessive or sustained reactive astrocytes can be deleterious to functional recovery or contribute to chronic inflammation and neuronal dysfunction. Therefore, astrocyte activation in response to damage is likely to be tightly regulated. Although factors that activate astrocytes have been identified, whether factors also exist that maintain astrocytes as nonreactive or reestablish their nonreactive state after containing damage remains unclear. By using loss- and gain-of-function genetic approaches, we show that, in the unperturbed adult neocortex, FGF signaling is required in astrocytes to maintain their nonreactive state. Similarly, after injury, FGF signaling delays the response of astrocytes and accelerates their deactivation. In addition, disrupting astrocytic FGF receptors results in reduced scar size without affecting neuronal survival. Overall, this study reveals that the activation of astrocytes in the normal and injured neocortex is not only regulated by proinflammatory factors, but also by factors such as FGFs that suppress activation, providing alternative therapeutic targets.
authors.affiliation: Departments of Neuroscience and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461;
authors.forename: Wenfei
authors.initials: W
authors.lastname: Kang
authors.affiliation: Departments of Cell Biology and Neural Science, Smilow Neuroscience Program, New York University Langone Medical Center, New York, NY 10016; and.
authors.forename: Francesca
authors.initials: F
authors.lastname: Balordi
authors.affiliation: Chongqing Daping Hospital, Third Millitary Medical University, Chongqing 400042, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Su
authors.affiliation: Chongqing Daping Hospital, Third Millitary Medical University, Chongqing 400042, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Departments of Cell Biology and Neural Science, Smilow Neuroscience Program, New York University Langone Medical Center, New York, NY 10016; and.
authors.forename: Gordon
authors.initials: G
authors.lastname: Fishell
authors.affiliation: Departments of Neuroscience and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461; jean.hebert@einstein.yu.edu.
authors.forename: Jean M
authors.initials: JM
authors.lastname: Hébert
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005838:Genotype; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D005904:Glial Fibrillary Acidic Protein; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors
keywords: astrogliosis; brain damage