Effects of lipid mediator, lysophosphatidic acid, on regenerating chick neurons

Abstract

The leading edge of growing and regenerating neuron, nerve growth cone, plays important roles in the regenerating process after neuronal injury. The nerve growth cones collapse when they encounter repulsive factors expressed in the surrounding tissues. Lysophosphatidic acid (LPA) is rapidly generated by activated platelets or by cells after tissue damage, and serves as an intercellular messenger. This lipid mediator caused growth cone collapse in primary cultured chick neurons. This action was dose dependent and the potency was almost identical in three different neuron types: dorsal root ganglion neurons, retinal neurons, and sympathetic ganglion cells. Fifty % of growth cones were collapsed by 10^-6 M LPA. The growth cone collapse started within 2 min after LPA exposure and no homologous desensitization was observed. However, this action was reversible and not toxic to the neurons. This result implied that LPA acts as an inhibitory factor of neurite growth after nerve injury in vivo. LPA antagonists seem to be promising as promoting substances of nerve regeneration.