In vitro differentiation inhibits the migration of cultured neonatal rat cortical astrocytes transplanted to the neonatal rat cerebrum.
Neonatal rat astrocytes transplanted into the rat cerebrum migrate extensively. However, few of the molecular signals determining this migration have been defined. In the present study, in vitro modifications were designed to examine whether differentiation prior to transplantation would affect the magnitude or pattern of astrocyte migration in the neonatal host brain. Here, cortical astrocytes were collected from the brains of rats 1-3 days postpartum and purified by culturing them in DME medium supplemented with 10% calf serum. After 14-21 days, astrocytes were labelled with fluorescein-tagged latex microspheres for 16 hr; the label was then removed and replaced with either fresh medium or fresh serum-free medium plus 1 mM dbcAMP. After 48 hr, cells were harvested and then transplanted into the right frontal cerebrum of neonatal rats at 3 days postpartum by injection with a hand-held Hamilton syringe. Animals were sacrificed at 3, 6, 9, 15, 21 and 28 days after inoculation and their brains examined with fluorescence microscopy. Astrocytes not exposed to dbcAMP prior to implantation migrated along the corpus callosum, internal capsule, glial limitans, ventricular linings and the hippocampal structure. They also appeared to migrate in a radial fashion toward the periphery from the ventricular lining. Astrocytes treated with dbcAMP prior to transplantation did not appear to migrate into the neonatal parenchyma, remaining confined to the injection site for at least 6 days. Migration then appeared to commence at a normal rate after 9 days. Thus, neonatal cortical migrate outward in a pattern similar to that defined by the radial glia. Astrocytes differentiated by dbcAMP treatment, however, do not appear to migrate to any large degree in the neonatal brain until the treatment effect diminishes, suggesting that differentiation may represent an end-point to glial migration in the neonatal host brain.
Hatton
J D
JD
Division of Neurosurgery, University of California at San Diego, La Jolla 92093.
Hoi
S U
SU
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000502:physiology*; D001921:Brain / Q000166:cytology*; D016380:Brain Tissue Transplantation / Q000502:physiology*; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D017690:Cell Transplantation / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D008863:Microspheres; D051381:Rats
D005904:Glial Fibrillary Acidic Protein; D003994:Bucladesine