CYTOSKELETAL PROTEIN IMMUNOEXPRESSION IN FETAL NEURAL GRAFTS - DISTRIBUTION OF PHOSPHORYLATED AND NONPHOSPHORYLATED NEUROFILAMENT PROTEIN AND MICROTUBULE-ASSOCIATED PROTEIN-2 (MAP-2)

The present study examined the immunocytochemical expression of import ant cytoskeletal proteins within the neurons of an extended series of neocortical grafts and smaller group of ventral mesencephalic (nigral) grafts. Using antibodies that were directed at all three neurofilamen t (NF) epitopes, NF-L, NF-M, and NF-H, we attempted to determine wheth er these neurons would have an altered cytoskeletal profile following the stress of transplantation, because previous studies have shown suc h changes following ischemia or direct brain injury. We studied phosph orylated NF protein, which is found predominantly in axons, nonphospho rylated NF protein, which is found predominantly in the somata-dendrit ic compartment, and MAP-2, a specific microtubule marker that is local ized exclusively in the somato dendritic compartment. The results show that in all neocortical grafts examined, both phosphorylated and nonp hosphorylated NF immunoexpression was significantly downregulated and appeared only in relatively few axons and somatic profiles, respective ly, even though there were numerous Nissl stained neuronal profiles in the grafts. There was no particular pattern to the immunopositive pro files. At later times occasional neuronal profiles were positive for p hosphorylated NF protein, suggesting a reaction to cellular injury. In contrast to neocortical grafts, the cytoskeletal profiles of MAP-2 an d phosphorylated NF protein in nigral grafts appeared very similar to age-matched control although the nonphosphorylated NF protein expressi on did appear somewhat lessened at 1-2 mo postoperative. Because cytos keletal proteins play important roles in neuronal size, shape, and str uctural stability, they may subserve key cellular issues in neural gra fting. These results show a significant loss of cytoskeletal protein e xpression in neocortical grafts that does not occur in nigral grafts. These results suggest that fetal neurons from different brain regions (i.e., graft source) may respond differently to the grafting procedure insofar as their cytoskeletal makeup is concerned. In addition, a pot ential lack of appropriate growth substrates or synaptic contacts may also produce cytoskeletal alterations. As such, the cytoskeletal prote in profiles in central nervous system (CNS) grafts may be useful marke rs for functional performance, perhaps reflecting a degree of cellular injury.