X-Message-Number: 984 Newsgroups: sci.cryonics From: (kevin.q.brown) Subject: The Difference Between Us and Salamanders Date: Mon, 14 Jul 1992 17:41:52 GMT Keywords: self-repair NCAMs [ One thing that is certain about cryonic suspension is that a lot of repair will be needed to reanimate anyone frozen with today's suspension methods. Some organisms, such as salamanders, have self-repair capabilities that may be useful to humans, if only we can figure out how to transfer those capabilities to humans. This message from a recent issue of Periastron describes progress in our understanding of how salamander's self-repair capability works. It is posted with permission of the author Thomas Donaldson <>. - KQB ] THE DIFFERENCE BETWEEN US AND SALAMANDERS by Thomas Donaldson Periastron, P.O. Box 2365, Sunnyvale, CA 94087 USA For many years now scientists have known that salamanders have far more ability to repair themselves than any human being. The most visible sign of this comes from their ability to regrow a tail or limb if one has been torn off. They have a similar ability, less visible, to repair their own brain if it has been cut and even scrambled a bit. For any application to medicine, some way to create those same abilities artificially in human beings would have tremendous benefits. Yet up to quite recently no one has even had a hint about just why such an extreme different exists. Means to help repair spinal cords and injured brains still seem far away, means to regrow a lost leg just as far. Recently however an interesting paper in NATURE (P Doherty, SV Ashton, CECK Moolenaar, and others, NATURE (356)(1992) 791-793) presents evidence about one chemical factor which may account for some of our repair inability. By now scientists have isolated several chemical factors which promote and guide growth in embryonic brains (and other tissue, too). One prominent class of such factors are the NCAMs (already discussed in this issue: see the first article). NCAM stands for Neural Cell Adhesion Molecule. NCAMs are a family of protein molecules which cause outer neuron surfaces to stick together. In embryos, they not only cause this sticking effect but actually promote and guide neuron growth, particularly the growth of processes out of the neural cell body (both dendrites and axons). NCAMs have one other distinguishing trait: rather like the immunoglobins in our immune system, their proteins sequence allows for variability. For NCAMs this means that each NCAM gene can produce 20 to 30 different proteins, depending on just how the NCAM protein is spliced together from its parts. The authors of this paper single out one gene part which (combined with the rest of the NCAM gene) can create a special form of NCAM 140. They call this the "Variable Alternatively Spliced Exon", or VASE (our genes consist of two kinds of sequences: introns, which may play a guiding role but don't actually act as a template for any part of the protein(s) the gene produces, and exons, which DO act as templates for a protein or part of one). Doherty, Ashton, Moolenaar, and their colleagues show, in their paper, two things. First, only about 3% of the NCAMs in embryonic brain tissue contained the VASE sequence, while 50% if NCAMs in adult brain contained it. By performing direct experiments on embryonic brain cells, they could show that NCAM-VASE would inhibit growth in embryonic cells too. That is, the change in NCAM type acts directly to inhibit growth. These experiments don't tell us just WHY our NCAMs change to the VASE type. They do tell us where to keep looking for the causes of our inhibited neural growth as adults. Furthermore, the authors of this paper point out that several other chemical factors must play an important role. Polysialic acid also occurs in growing embryonic brain, and seems to modulate the effect of NCAMs, VASE or not. Other factors in embryonic brain also promote neuron growth, among which are N-cadherin and integrin. As with many phenomena in our nervous system, calcium ions play a role in growth, too. While these NCAM-VASEs show much less ability to promote growth, they still play an important role in adult nervous systems. Their adhesive ability remains unchanged. They act in this way to hold together the final form of our brain. In embryonic brain, their influence on growth seems to act indirectly, through biochemical effects on other processes rather than through simple adhesion. Their role in growth, development, and its inhibition needs much more exploration. This paper points to a direction for that exploration. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=984