The OM series of terminal field-specific monoclonal antibodies demonstrate reinnervation of the adult rat dentate gyrus by embryonic entorhinal transplants.
Monoclonal antibodies OM-1 to OM-4 and IM-1 [Woodhams et al. (1991) Neuroscience 46, 57-69] have complementary immunostaining patterns in the molecular (dendritic) layer of the adult rat dentate gyrus, with OM-1 to OM-4 selectively recognizing the outer (distal) two-thirds (i.e. the entorhinal afferent zone), and IM-1 the inner (proximal) one-third (i.e. the hippocampal commissural/associational zone). Immunoblotting suggests that OM-1 recognizes a single glycoprotein antigen of mol. wt around 93,000, and OM-2, OM-3, and OM-4 all recognize a second glycoprotein antigen of mol. wt around 36,000. At four weeks after removal of the ipsilateral entorhinal cortex the background OM immunostaining of the entorhinal afferent zone is abolished and replaced by a network of densely stained granules, which we interpret as degenerating entorhinal afferent axons. At the same time, the proximal, IM immunoreactive zone expands by about 10 microns in width (while the distal deafferented zone shrinks by about 80 microns). Attempts were made to restore the OM immunoreactivity of the distal zone by grafting either small pieces or cell suspensions of embryonic day 18 entorhinal cortex directly into the dentate molecular layer of entorhinally deafferented adult hosts. About half (14/26) of the animals with successfully positioned grafts showed restoration of OM-2 to OM-4 immunostaining throughout the entire width of the outer two-thirds (entorhinal afferent zone) of the dentate molecular layer. Strikingly, however, in adjacent serial sections the restoration of OM-1 immunoreactivity was restricted to the "middle" molecular layer, i.e. the most proximal part of the distal (entorhinal) two-thirds of the dentate molecular layer. In no case did the OM-1 immunoreactivity extend to the outer margin of the molecular layer. This did not appear to be associated with incompleteness of the removal of the host entorhinal projection, since it occurred in grafted cases where the hippocampus had been completely isolated from the entorhinal area. The simplest explanation of the observed pattern of OM loss and restitution is that the epitopes are located on the entorhinodentate axons, but it is not clear whether the antigens recognized by OM-1 and OM-2 to OM-4 are expressed in different parts of the same group of axons, or in different subsets of entorhinodentate axons. Nor is it clear why the pattern of OM-1 is only restored to the "middle" molecular layer, while that of OM-2 to OM-4 is restored to the entire outer two-thirds.(ABSTRACT TRUNCATED AT 400 WORDS)
Woodhams
P L
PL
Norman and Sadie Lee Research Centre, National Institute for Medical Research, London, U.K.
Kawano
H
H
Raisman
G
G
D000818:Animals; D000911:Antibodies, Monoclonal; D001369:Axons / Q000276:immunology; D016380:Brain Tissue Transplantation / Q000502:physiology; D000939:Epitopes / Q000276:immunology; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology; D006624:Hippocampus / Q000166:cytology* / Q000276:immunology; D007150:Immunohistochemistry; D009410:Nerve Degeneration / Q000502:physiology; D009411:Nerve Endings / Q000166:cytology* / Q000276:immunology; D009475:Neurons, Afferent / Q000648:ultrastructure; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D000911:Antibodies, Monoclonal; D000939:Epitopes