Amputation Injury Is Communicated to Opposing Limb

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Bioelectric depolarization is indicated using a fluorescent dye (brighter green areas). Depolarization patterns in the uninjured leg (right) occur within seconds of amputation of the opposing leg (left), reflecting both the position and type of injury. Yellow arrow points to spinal cord.

Photograph courtesy of Sera Busse, Patrick McMillen, Michael Levin - Tufts University.

In research that extends knowledge about limb regeneration and wound repair, biologists at Tufts University have discovered that amputation of one limb is immediately reflected in the bioelectric properties of the contralateral, undamaged limb of developing frogs. A pattern of bioelectric depolarization in the uninjured leg is directly correlated to the position and type of injury, indicating that information about damage to tissues is available to the symmetrical counterpart within about 30 seconds of injury. The newly discovered phenomenon, called bioelectric injury mirroring, is described in the October issue of the journal Development.

Bioelectric states, in which charged ions move in or out of a cell, have previously been implicated in regeneration, and researchers have been able to alter bioelectric states to induce the regeneration of tails on tadpoles that had already matured beyond the capability of regeneration.

Sera Busse, the study's first author who conducted the research as an undergraduate student, Patrick McMillen, PhD, and Michael Levin, PhD, devised experiments using a fluorescent dye to reveal the pattern of electrical depolarization in the upper layer of skin. When Busse amputated the limbs of froglets still in the regeneration stage, the dye revealed that the uninjured leg exhibited bioelectric states that mirrored the location and type of injury occurring on the opposite side, and the effect was immediate, occurring within five seconds.

"What was amazing about this result was that not only did the depolarization in the uninjured leg detect the presence of injury on the other side, it also reflected information about the position of the cut," said Levin.

The researchers considered whether such information was conveyed by typical neural communication through the central nervous system or spinal cord, but the signal was undiminished when the central nervous system communication was interrupted. The result suggests that the distant communication between limbs occurs by a cell-to-cell mechanism, according to the researchers.