Reactive astrogliosis induces astrocytic differentiation of adult neural stem/progenitor cells in vitro.

• Neural stem cells reside in defined areas of the adult mammalian brain, including the dentate gyrus of the hippocampus. Rat neural stem/progenitor cells (NSPCs) isolated from this region retain their multipotency in vitro and in vivo after grafting into the adult brain. Recent studies have shown that endogenous or grafted NSPCs are activated after an injury and migrate toward lesioned areas. In these areas, reactive astrocytes are present and secrete numerous molecules and growth factors; however, it is not currently known whether reactive astrocytes can influence the lineage selection of NSPCs. We investigated whether reactive astrocytes could affect the differentiation, proliferation, and survival of adult NSPCs by modelling astrogliosis in vitro, using mechanical lesion of primary astrocytes. Initially, it was found that conditioned medium from lesioned astrocytes induced astrocytic differentiation of NSPCs without affecting neuronal or oligodendrocytic differentiation. In addition, NSPCs in coculture with lesioned astrocytes also displayed increased astrocytic differentiation and some of these NSPC-derived astrocytes participated in glial scar formation in vitro. When proliferation and survival of NSPCs were analyzed, no differential effects were observed between lesioned and nonlesioned astrocytes. To investigate the molecular mechanisms of the astrocyte-inducing activity, the expression of two potent inducers of astroglial differentiation, ciliary neurotrophic factor and leukemia inhibitory factor, was analyzed by Western blot and shown to be up-regulated in conditioned medium from lesioned astrocytes. These results demonstrate that lesioned astrocytes can induce astroglial differentiation of NSPCs and provide a mechanism for astroglial differentiation of these cells following brain injury.

Nyckelord

Analysis of Variance

Animals

Astrocytes

physiology

Blotting

Western

methods

Brain Injuries

physiopathology

surgery

Cell Count

methods

Cell Differentiation

physiology

Cell Movement

physiology

Cell Proliferation

Ciliary Neurotrophic Factor

metabolism

Dentate Gyrus

cytology

Glial Fibrillary Acidic Protein

metabolism

Green Fluorescent Proteins

metabolism

Immunohistochemistry

methods

Intermediate Filament Proteins

metabolism

Leukemia Inhibitory Factor

metabolism

Nerve Tissue Proteins

metabolism

Neurons

physiology

Rats

Stem Cell Transplantation

Stem Cells

physiology

Thymidine

metabolism

Transfection

methods

Tritium

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)