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

• Published in: Journal of neuroscience research Vol. 84; no. 7; pp. 1415 - 1424
• Main Authors: Faijerson, J., Tinsley, R.B., Apricó, K., Thorsell, A., Nodin, C., Nilsson, M., Blomstrand, F., Eriksson, P.S.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.11.2006
• Subjects: Analysis of Variance; Animals; Astrocytes; Astrocytes - physiology; astroglia; Blotting; Blotting, Western - methods; Brain Injuries; Brain Injuries - physiopathology; Brain Injuries - surgery; Cell Count; Cell Count - methods; Cell Differentiation; Cell Differentiation - physiology; Cell Movement; Cell Movement - physiology; Cell Proliferation; Ciliary Neurotrophic Factor; Ciliary Neurotrophic Factor - metabolism; cytology; Dentate Gyrus; Dentate Gyrus - cytology; Glial Fibrillary Acidic Protein; Glial Fibrillary Acidic Protein - metabolism; Green Fluorescent Proteins; Green Fluorescent Proteins - metabolism; Immunohistochemistry; Immunohistochemistry - methods; In Vitro Techniques; Intermediate Filament Proteins; Intermediate Filament Proteins - metabolism; Leukemia Inhibitory Factor; Leukemia Inhibitory Factor - metabolism; MEDICAL AND HEALTH SCIENCES; MEDICIN OCH HÄLSOVETENSKAP; metabolism; methods; Nerve Tissue Proteins; Nerve Tissue Proteins - metabolism; Nestin; neural progenitors; neural stem cells; neurogenesis; Neurons; Neurons - physiology; physiology; physiopathology; Rats; reactive astrocytes; Stem Cell Transplantation; Stem Cells; Stem Cells - physiology; surgery; Thymidine; Thymidine - metabolism; Transfection; Transfection - methods; Tritium; Tritium - metabolism; Western
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.21044

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. © 2006 Wiley‐Liss, Inc.