The astrocytic lineage marker calmodulin-regulated spectrin-associated protein 1 (Camsap1): phenotypic heterogeneity of newly born Camsap1-expressing cells in injured mouse brain

J Comp Neurol. 2012 Apr 15;520(6):1301-17. doi: 10.1002/cne.22788.

Abstract

Calmodulin-regulated spectrin-associated protein 1 (Camsap1) has been recognized as a new marker for astrocytic lineage cells and is expressed on mature astrocytes in the adult brain (Yamamoto et al. [2009] J. Neurosci. Res. 87:503–513). In the present study, we found that newly born Camsap1-expressing cells exhibited regional heterogeneity in an early phase after stab injury of the mouse brain. In the surrounding area of the lesion site, Camsap1 was expressed on quiescent astrocytes. At 3 days after injury, Camsap1 immunoreactivity was upregulated on glial fibrillary acidic protein-immunoreactive (GFAP-ir) astrocytes. Some of these astrocytes incorporated bromodeoxyuridine (BrdU) together with re-expression of the embryonic cytoskeleton protein nestin. In the neighboring region of the lesion cavity, Camsap1 was expressed on GFAP-negative cells. At 3 days after injury, GFAP-ir astrocytes were absent around the lesion cavity. At this stage, NG2-ir cells immunopositive for Camsap1 and immunonegative for GFAP were distributed in border of the lesion cavity. By 10 days, Camsap1 immunoreactivity was exclusively detected on GFAP-ir reactive astrocytes devoid of NG2 immunoreactivity. BrdU pulse-chase labeling assay suggested the differentiation of Camsap1+/NG2+ cells into Camsap1+/GFAP+ astrocytes. In the subependymal zone of the lateral ventricle, Camsap1-ir cells increased after injury. Camsap1 immunoreactivity was distributed on ependymal and subependymal cells bearing various astrocyte markers, and BrdU incorporation was enhanced on such Camsap1-ir cells after injury. These results suggest that newly born reactive astrocytes are derived from heterogeneous Camsap1-expressing cells in the injured brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Biomarkers / metabolism
  • Brain Injuries / genetics
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology
  • Calmodulin / physiology*
  • Cell Lineage / genetics
  • Cytoskeletal Proteins
  • Gliosis / genetics
  • Gliosis / metabolism*
  • Gliosis / pathology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics*
  • Phenotype
  • Spectrin / biosynthesis
  • Spectrin / genetics*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Stem Cells / pathology
  • Up-Regulation / genetics

Substances

  • Biomarkers
  • Calmodulin
  • Camsap1 protein, mouse
  • Cytoskeletal Proteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Spectrin