Presenilin-1 and its N-terminal and C-terminal fragments are transported in the sciatic nerve of rat

The axonal transport of presenilin-1 was investigated in a spinal cord-scia tic nerve-neuromuscular junction model system in the rat. The technique of unilateral sciatic nerve ligation, using double ligatures, was combined wit h immunohistochemical staining and Western blotting to examine the axonal t ransport of the protein. Immunohistochemical studies involving the use of p olyclonal antibodies for either the N-terminal or the C-terminal domain of presenilin-1 furnished evidence that both fragments may be present not only in the neuronal cell bodies, but also in the motoric and sensory axons and the motoric axon terminals at the neuromuscular junctions. After double li gation of the sciatic nerve for 6, 12 or 24 h, progressive immunostaining o f presenilin-1 occurred above the upper ligature and to a lesser extent bel ow the lower ligature. Double staining of the sciatic nerve for presenilin- 1 and for amyloid precursor protein revealed overlapping immunoreactivity. Western blotting confirmed the accumulation of the similar to 20-kDa C-term inal and similar to 25-kDa N-terminal fragments and the full-length 45-kDa holoprotein of presenilin-1 both above and below the ligature. It is conclu ded that besides the larger amounts of C-terminal and N-terminal fragments, a smaller quantity of intact presenilin-1 may be present and conveyed bidi rectionally in the sciatic nerve of the rat. These results lend further sup port to the suggestion that presenilin-1 may leave the trans-Golgi network and be found in the axons and axon terminals of the various neurons. (C) 20 01 Elsevier Science B.V. All rights reserved.