Sialic acid is attached to the end of the chains of sugars such as glycoconjugates on the cell membrane, and is also abundant in the CNS. Endogenous sialidases are glycosidases that hydrolyze a glycosylated sialic acid residue from carbohydrate groups of glycoconjugates. Dysfunction of the CNS, such as extrapyramidal disturbance and intellectual impairment, results from the loss of function or deficiencies of endogenous sialidases. CNS functions are regulated through the neural network by neurite outgrowth and regression, so focusing on the mechanism of outgrowth, it is reasonable to think about the role of sialidases in the CNS. Neurite outgrowth is induced by lots kinds of growth factors, one of which is insulin. It has been reported that insulin possesses the growth potential of neurite. Insulin enhances endogenous sialidase activity, enhancing the intracellular insulin signaling through desialylation in the insulin receptor in rat myoblasts. Although endogenous sialidases are expressed in neurons, it is not clear what kind of CNS function or events are associated with its activity. Therefore, to clarify the functions of endogenous sialidases in the CNS, in this study, we examined the effect of endogenous sialidases on neurite outgrowth induced by a growth factor such as insulin.
Treatment with insulin or IGF-I (insulin like growth factor I) extended the neurite length of SH-SY5Y (human neuroblastoma) cells in a dose dependent manner. The effect of insulin on neurite outgrowth was significantly inhibited by the pre-treatment with 1 mM of sialidase inhibitor, DANA (2,3-dehydro-3-deoxy-N-acetylneuraminic acid). Moreover, treatment with sialidase, without any insulin receptor ligand, also extended neurite length of SH-SY5Y cells. We also examined the role of endogenous sialidases during the period of neural circuitry formation in rats. Cerebral ventricular administration of DANA (1 mM, 5 μL) increased the spontaneous behavior distance in 3 week-old rats, but no increase was observed in 8 week-old rats. These results suggest that insulin-induced neurite outgrowth and normal locomotor function in the neural circuit formation period are associated with endogenous sialidase activity.