Repetitive spreading depression induces nestin protein expression in the cortex of rats and mice. Is this upregulation initiated by N-methyl-D-aspartate receptors?

In the November issue (2001) of Neuroscience Letters, Holmin et al. (Neurosci. Lett. 314 (2001) 151) reported that the synthesis of the intermediate filament protein nestin was upregulated by potassium-induced depolarization in the rat cortex. In this letter, we provide supplementary evidence that repeated cortical spreading depression elicited by potassium induces a delayed upregulation of nestin. However, we argue against the authors' conclusion, "Nestin expression was N-methyl-D-aspartate (NMDA)-receptor dependent since dizocilpine (MK-801) treatment abolished the response" because spreading depression itself is very sensitive to NMDA-receptor block, and the drug treatment was initiated prior to potassium application to the cortex in Holmin et al.'s study.