6-Hydroxydopamine induced ectopia of external granule cells in the subarachnoid space covering the cerebellum. II. Differentiation of granule cells: a scanning and transmission electron microscopic study.
The present report describes the morphological differentiation of ectopic granule cells from external granule cells that have been induced to escape from the cerebellar cortex into the subarachnoid space by injecting neonatal rats with 100 microgram 6-hydroxydopamine (6-OHDA) into the cisterna magna. The following cell types were observed in the period between 5 and 25 days postinjection (dpi): (1) unipolar cells with one process bearing a growth cone at its tip; (2) bipolar cells with two thin beaded processes originating from opposite cell poles, bearing growth cones at their tips; (3) bipolar cells with a T-like process at one pole and a short process lacking a terminal growth cone at the opposite pole; (4) multipolar cells with one thin beaded process and two or more short processes bearing growth cones of a different morphology at their tips; (5) intermediate stages. In the late second week p.i., cell aggregates were observed that continually increased in size up to 30 dpi. On the basis of our light, transmission, and scanning electron microscopic findings, we interpret these cell types to be equivalent to the individual stages of granule cell differentiation that characterize axon formation, migration, and aggregation. In the period between 30 and 365 dpi, granule cells were almost exclusively organized into cell colonies of different sizes, but small cell clusters and single granule cells exhibited the scanning electron microscopic features of adult granule cells, i.e., a small spherical cell body, a single axon with parent axonal stem, T-junction, and parallel fiber, and dendrites engaged in synaptic glomeruli. The parallel fibers ran in fasciculi of different sizes, often parallel to each other, but without preferential orientation over the cerebellar surface. During migration and aggregation, the granule cells and their processes were associated with a substrate of glial sheets that in turn were connected to intracortical Bergmann glia fibers. Our findings indicate that (1) granule cells differentiate normally in an ectopic environment in the presence of glia, (2) ectopic Bergmann glia contain no directional information to guide aberrant migratory granule cells to their correct destination, (3) granule cells can survive outside the brain parenchyma for periods up to one year (the longest postinjection interval studied).
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002465:Cell Movement; D002525:Cerebellar Cortex / Q000166:cytology* / Q000648:ultrastructure; D006892:Hydroxydopamines / Q000494:pharmacology*; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D013346:Subarachnoid Space
D006892:Hydroxydopamines; D016627:Oxidopamine