Oleic acid synthesized in the periventricular zone promotes axonogenesis in the striatum during brain development.
Our previous works showed that oleic acid synthesized in vitro by astrocytes in response to albumin behaves as a neurotrophic factor in neurons, up-regulating several proteins, such as the axonal growth marker growth-associated protein 43(GAP-43). Although the molecular mechanism of this process is fairly known, there is no evidence pinpointing the region/s in which oleic acid is synthesized. In this study, we show that the rate-limiting enzyme in oleic acid synthesis, stearoyl-CoA desaturase (SCD-1), is located in the periventricular zone of the brain of newborn rats, simultaneously to an increase in the amount of free oleic acid in the forebrain. In addition, the spatio-temporal presence of albumin - the signal that promotes oleic acid synthesis - and that of GAP-43 are correlated with that of SCD-1. Using organotypic slice cultures, we found that albumin up-regulates SCD-1 and stimulates the growth of GAP-43-positive axons in the striatum. The effect of albumin on GAP-43 was reduced when SCD-1 was silenced by siRNA. In conclusion, our results suggest that albumin up-regulates axonogenesis in the striatum by increasing the amount of the neurotrophic factor oleic acid synthesized by SCD-1 in the periventricular zone of the newborn brain.
Polo-Hernández
Erica
E
Departamento de Bioquímica y Biología Molecular, Instituto de Neurociencias de Castilla y León, INCYL, Universidad de Salamanca, Salamanca, Spain.
De Castro
Fernando
F
García-García
Alejandro G
AG
Tabernero
Arantxa
A
Medina
José M
JM
D000418:Albumins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D002552:Cerebral Ventricles / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D003342:Corpus Striatum / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D019922:GAP-43 Protein / Q000096:biosynthesis; D018507:Gene Expression Regulation, Developmental; D019301:Oleic Acid / Q000096:biosynthesis*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques
D000418:Albumins; D019922:GAP-43 Protein; D034741:RNA, Small Interfering; D019301:Oleic Acid; D013230:Stearoyl-CoA Desaturase