4.7 Article

Creatine pretreatment protects cortical axons from energy depletion in vitro

期刊

NEUROBIOLOGY OF DISEASE
卷 47, 期 2, 页码 184-193

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2012.03.037

关键词

Creatine; Energy depletion; Ischemia; Axonal injury; ATP; White matter; Compartmental culture

资金

  1. NIH Neuroscience Blueprint Interdisciplinary Center Core Grant [P30 NS057105]
  2. NIH [P01 NS032636, R01 NS036265]

向作者/读者索取更多资源

Creatine is a natural nitrogenous guanidino compound involved in bioenergy metabolism. Although creatine has been shown to protect neurons of the central nervous system (CNS) from experimental hypoxia/ischemia, it remains unclear if creatine may also protect CNS axons, and if the potential axonal protection depends on glial cells. To evaluate the direct impact of creatine on CNS axons, cortical axons were cultured in a separate compartment from their somas and proximal neurites using a modified two-compartment culture device. Axons in the axon compartment were subjected to acute energy depletion, an in vitro model of white matter ischemia, by exposure to 6 mM sodium azide for 30 min in the absence of glucose and pyruvate. Energy depletion reduced axonal ATP by 65%, depolarized axonal resting potential, and damaged 75% of axons. Application of creatine (10 mM) to both compartments of the culture at 24 h prior to energy depletion significantly reduced axonal damage by 50%. in line with the role of creatine in the bioenergy metabolism, this application also alleviated the axonal ATP loss and depolarization. Inhibition of axonal depolarization by blocking sodium influx with tetrodotoxin also effectively reduced the axonal damage caused by energy depletion. Further study revealed that the creatine effect was independent of glial cells, as axonal protection was sustained even when creatine was applied only to the axon compartment (free from somas and glial cells) for as little as 2 h. In contrast, application of creatine after energy depletion did not protect axons. The data provide the first evidence that creatine pretreatment may directly protect CNS axons from energy deficiency. (C) 2012 Elsevier Inc. All rights reserved.

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