Late axonal sprouting of injured Purkinje cells and its temporal correlation with permissive changes in the glial scar.
Purkinje cells can survive axotomy for as long as 18 months without retracting their severed axons. During this period of time, the fate of the terminal bulbs of axotomized Purkinje cell axons and their relationship with the glial scar were determined. Terminal axonal sprouting begins three months after the lesion and continuously increases up to 18 months (the longest survival time studied), when the sprouts establish synaptic contacts, mainly on granule cell dendrites at the glomeruli. Cellular changes in the glial scar were analyzed to determine whether the late onset and continuous increase of axonal sprouting could be correlated with an increase of permissive factors and/or a decrease of inhibitory factors for axonal growth. Activated macrophages disappeared much earlier than did the initiation of sprouting. Myelin and its associated neurite growth inhibitory molecules began to decrease from three months after the lesion. This decrease was uneven and not correlated spatially with the sprouting. Reactive astrogliosis was heterogeneous: only some of the reactive astrocytes expressed PSA-NCAM, the embryonic form of the neural cell adhesion molecule, a permissive substratum for neurite outgrowth. The expression of PSA-NCAM occurred concurrently with sprouting in the area of gliosis containing Purkinje cell sprouts. Moreover, the ultrastructural study showed that the majority of sprouts (75%) were totally ensheathed by astrocytic processes. Thus, long-term glial scars are permissive to axonal sprouting, suggesting that reactive astrocytes, either through the expression of permissive molecules or by preventing direct contact between axonal elements and myelin inhibitory molecules, regulate the sprouting.
Dusart
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I
INSERM U106, Hôpital de la Salpêtrière, Paris, France. dusart@infobiogen.fr
Morel
M P
MP
Wehrlé
R
R
Sotelo
C
C
D000818:Animals; D001369:Axons / Q000502:physiology*; D019771:Axotomy; D002531:Cerebellum / Q000502:physiology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D004676:Myelin Basic Protein / Q000096:biosynthesis; D009416:Nerve Regeneration; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis; D009457:Neuroglia / Q000502:physiology; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012794:Sialic Acids / Q000096:biosynthesis; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule