Positive injury signals induce growth and prolong survival in Aplysia neurons

Injury to a peripheral nerve initiates changes that can lead to regeneratio n of the damaged axons. How information about a distant injury is communica ted to the cell body is not clear. Using the nervous system of Aplysia cali fornica, we tested the idea that some of this information is conveyed via p ositive injury signals-axoplasmic proteins that are activated at the injury site and transported to the cell soma. We collected these proteins by crus hing pedal nerves and then placing a ligation proximal to the ligation. The contralateral nerves were ligated as controls. Twenty h later, axoplasm wa s extruded from the nerve segment just distal to the ligation on the crushe d nerves (cr/lig) and on the control nerves (lig). The total proteins were rhodaminated and injected into the cytoplasm of neurons in vitro to look fo r nuclear import. Punctate fluorescence was detected in the nucleus of all seven neurons injected with the cr/lig axoplasm. Only two of five neurons i njected with lig axoplasm had any fluorescence. Equal amounts of cr/lig and lig axoplasm were then injected directly into the cell bodies of neurons m aintained in vitro. The cells injected with cr/lig axoplasm exhibited renew ed growth and significantly longer survival: 25.9 +/- 2.1 days (mean +/- SE M: n = 22) relative to the cells injected with lig axoplasm (15.3 +/- 1.2 d ays; n = 14) and to those that were not injected (12.2 +/- 1.7 days; n = 24 ). Fractionation of the cr/lig axoplasm indicated that different factors ar e responsible for growth and survival. (C) 2000 John Wiley & Sons, Inc.