Action mechanisms of galectin-1, CNTF and phosphacan for the regulation of axonal regeneration

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We investigated the action mechanisms of growth-promoting molecules such as oxidized galectin-1 and ciliary neurotrophic factor (CNTF) and regulatory molecules such as chondroitin sulfate proteoglycans (especially phosphacan) in axonal regeneration after injury.(1)Galectin-1 and CNTF : Immunohistochemistry on the sections of adult rat dorsal root ganglia (DRG) revealed that galectin-1 was abundantly expressed in small-diameter sensory neurons and Schwann cells while CNTF expression was restricted to Schwann cells. In contrast to the findings in vivo, we observed intense immunoreactivity for both galectin-1 and CNTF in DRG neurons after 3 hours, 2 days and 7 days in culture. At later stages of culture, the immunoreactivity was detected in regenerating neurites. These results suggest that both molecules are synthesized and transported to neurites in cultured DRG neurons. In spite of lacking signal leading sequences, galectin-1 is likely to be externalized from intact DRG neurons and Schw … More ann cells through the non-classical secretory pathway, whereas CNTF appears to be released from disrupted Schwann cells after peripheral nerve injury. Galectin-1 converted from the reduced form to the oxidized form in the extracellular space is likely to stimulate macrophages to secrete several factors (e.g. interleukin-6, bran derived neurotrophic factor), while CNTF directly acts on DRG neurons to activate signal transduction pathways (e.g. JAK-STAT3, MEK-MAPK, PI3K-Akt).(2)Chondroitin sulfate proteoglycans : Phosphacan purified from embryonic (E20) or postnatal (P7, P20) rat brain impaired attachment and neurite outgrowth of cultured adult rat DRG neurons. These inhibitory effects were dependent on dose (10μg/ml>1μg/ml>>0.1μg/ml) and age of rats from which the molecule was purified (P20>P7>E20). Since the structure of chondroitin sulfate of these preparations are immunologically and compositionally different, these findings suggest that variation of chondroitin sulfate chains plays important roles in the regulatory actions of phosphacan. Less