Cargando…

Lactate transport facilitates neurite outgrowth

How glia affect neurite outgrowth during neural development has not been well elucidated. In the present study, we found that disruption of lactate production using 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) and isofagomine significantly interfered with neurite outgrowth and that exogenous application...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Kun, Cheng, Peng, Wang, Huan, Gao, Shutao, Li, Xiao, Deng, Zhenhan, Liu, Jian, Sun, Xuying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167502/
https://www.ncbi.nlm.nih.gov/pubmed/30143583
http://dx.doi.org/10.1042/BSR20180157
Descripción
Sumario:How glia affect neurite outgrowth during neural development has not been well elucidated. In the present study, we found that disruption of lactate production using 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) and isofagomine significantly interfered with neurite outgrowth and that exogenous application of L-lactate rescued neurite growth failure. Monocarboxylate transporter-2-knockout, which blocked the lactate shuttle in neurons, showed a remarkable decrease in the length of axons and dendrites. We further demonstrated that Akt activity was decreased while glycogen synthase kinase 3β (GSK3β) activity was increased after astrocytic glycogen phosphorylase blockade. Additionally, GSK3βSer9 mutation reversed neurite growth failure caused by DAB and isofagomine. Our results suggested that lactate transportation played a critical role in neural development and disruption of the lactate shuttle in quiescent condition also affected neurite outgrowth in the central nervous system.